A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
A cell line derived from cultured tumor cells.
Agents that inhibit PROTEIN KINASES.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. Aberrant expression of this protein has been associated with deregulated EPITHELIAL CELL growth, organ enlargement, and a variety of NEOPLASMS.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Established cell cultures that have the potential to propagate indefinitely.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been associated with TESTICULAR CANCER.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Elements of limited time intervals, contributing to particular results or situations.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
BENZOIC ACID amides.
The rate dynamics in chemical or physical systems.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Chromones are a class of chemical compounds that contain a benzopyran-4-one core structure, which are found in various natural and synthetic substances, including some medications used to treat asthma and allergies.

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/2439)

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules.  (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (2/2439)

To investigate the mode of action of the p16(INK4a) tumor suppressor protein, we have established U2-OS cells in which the expression of p16(INK4a) can be regulated by addition or removal of isopropyl-beta-D-thiogalactopyranoside. As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. However, induction of p16(INK4a) also causes marked inhibition of CDK2 activity. In the case of cyclin E-CDK2, this is brought about by reassortment of cyclin, CDK, and CDK-inhibitor complexes, particularly those involving p27(KIP1). Size fractionation of the cellular lysates reveals that a substantial proportion of CDK4 participates in active kinase complexes of around 200 kDa. Upon induction of p16(INK4a), this complex is partly dissociated, and the majority of CDK4 is found in lower-molecular-weight fractions consistent with the formation of a binary complex with p16(INK4a). Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 by p27(KIP1) and p21(CIP1). Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6.  (+info)

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (3/2439)

The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens.  (+info)

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. (4/2439)

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.  (+info)

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. (5/2439)

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.  (+info)

Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human malignant melanoma. (6/2439)

Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor aggressiveness. We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. Instead, IL-6 caused a marked induction of the cdk inhibitor p21WAF1/CIP1 in three different IL-6 sensitive cell lines, two of which also showed a marked accumulation of the cdk inhibitor p27Kip1. In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. In fact, of five IL-6 resistant cell lines, only two expressed detectable levels of p21WAF1/CIP1 mRNA and protein, while in three other lines, p21WAF1/CIP1 was undetectable. IL-6 dependent upregulation of p21WAF1/CIP1 was associated with binding of both STAT3 and STAT1 to the p21WAF1/CIP1 promoter. Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. In somatic cell hybrids of IL-6 sensitive and resistant cell lines, the resistant phenotype was dominant and IL-6 failed to induce p21WAF1/CIP1. Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event.  (+info)

p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. (7/2439)

p27kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-beta. Since the cloning of the p27 gene in 1994, a host of other functions have been associated with this cell cycle protein. In addition to its role as a CDKI, p27 is a putative tumor suppressor gene, regulator of drug resistance in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mainly at the post-translational level with protein degradation by the ubiquitin-proteasome pathway. A large number of studies have characterized p27 as an independent prognostic factor in various human cancers, including breast, colon, and prostate adenocarcinomas. Here we review the role of p27 in the regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development.  (+info)

p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. (8/2439)

The cyclin-dependent kinase inhibitor p27Kip1 has been implicated as a drug resistance factor in tumor cells grown as spheroids or confluent monolayers. Here, we show that p27Kip1 overexpression also induces resistance to drug-induced apoptosis and cytotoxicity in human leukemic cells growing in suspension. The anti-apoptotic effect of p27Kip1 is not restricted to DNA-damaging agents but extends to the tubulin poison vinblastin, agonistic anti-Fas antibodies and macromolecule synthesis inhibitors. To further identify at which level this protein interferes with the cell death pathway, we investigated its influence on caspase activation and mitochondrial changes. Exposure of mock-transfected U937 cells to 50 microm etoposide activates procaspase-3 and the long isoform of procaspase-2 and induces mitochondrial potential decrease and cytochrome c release from mitochondria to the cytosol. All these events are prevented by p27Kip1 overexpression. p27Kip1 does not modulate Bcl-2, Bcl-X(L), Mcl-1 and Bax protein level in leukemic cells but suppresses Mcl-1 expression decrease observed in mock-transfected U937 cells undergoing etoposide-induced cell death. We conclude that p27Kip1 prevents cell death upstream of the final pathway common to many apoptotic stimuli that involves cytochrome c release from mitochondria and activation of downstream caspases.  (+info)

Cyclin-Dependent Kinase Inhibitor p27, also known as CDKN1B or p27Kip1, is a protein that regulates the cell cycle. It inhibits the activity of certain cyclin-dependent kinases (CDKs), which are enzymes that play key roles in regulating the progression of the cell cycle.

The cell cycle is a series of events that cells undergo as they grow and divide. Cyclins and CDKs help to control the different stages of the cell cycle by activating and deactivating various proteins at specific times. The p27 protein acts as a brake on the cell cycle, preventing cells from dividing too quickly or abnormally.

When p27 binds to a CDK-cyclin complex, it prevents the complex from phosphorylating its target proteins, which are necessary for the progression of the cell cycle. By inhibiting CDK activity, p27 helps to ensure that cells divide only when the proper conditions are met.

Mutations in the CDKN1B gene, which encodes p27, have been associated with several types of cancer, including breast, lung, and prostate cancer. These mutations can lead to decreased levels of p27 or impaired function, allowing cells to divide uncontrollably and form tumors.

Cyclin-dependent kinase inhibitor p21, also known as CDKN1A or p21/WAF1/CIP1, is a protein that regulates the cell cycle. It inhibits the activity of cyclin-dependent kinases (CDKs), which are enzymes that play crucial roles in controlling the progression of the cell cycle.

The binding of p21 to CDKs prevents the phosphorylation and activation of downstream targets, leading to cell cycle arrest. This protein is transcriptionally activated by tumor suppressor protein p53 in response to DNA damage or other stress signals, and it functions as an important mediator of p53-dependent growth arrest.

By inhibiting CDKs, p21 helps to ensure that cells do not proceed through the cell cycle until damaged DNA has been repaired, thereby preventing the propagation of potentially harmful mutations. Additionally, p21 has been implicated in other cellular processes such as apoptosis, differentiation, and senescence. Dysregulation of p21 has been associated with various human diseases, including cancer.

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that play crucial roles in regulating the cell cycle, transcription, and other cellular processes. They are activated by binding to cyclin proteins, which accumulate and degrade at specific stages of the cell cycle. The activation of CDKs leads to phosphorylation of various downstream target proteins, resulting in the promotion or inhibition of different cell cycle events. Dysregulation of CDKs has been implicated in several human diseases, including cancer, and they are considered important targets for drug development.

Cyclins are a family of regulatory proteins that play a crucial role in the cell cycle, which is the series of events that take place as a cell grows, divides, and produces two daughter cells. They are called cyclins because their levels fluctuate or cycle during the different stages of the cell cycle.

Cyclins function as subunits of serine/threonine protein kinase complexes, forming an active enzyme that adds phosphate groups to other proteins, thereby modifying their activity. This post-translational modification is a critical mechanism for controlling various cellular processes, including the regulation of the cell cycle.

There are several types of cyclins (A, B, D, and E), each of which is active during specific phases of the cell cycle:

1. Cyclin D: Expressed in the G1 phase, it helps to initiate the cell cycle by activating cyclin-dependent kinases (CDKs) that promote progression through the G1 restriction point.
2. Cyclin E: Active during late G1 and early S phases, it forms a complex with CDK2 to regulate the transition from G1 to S phase, where DNA replication occurs.
3. Cyclin A: Expressed in the S and G2 phases, it associates with both CDK2 and CDK1 to control the progression through the S and G2 phases and entry into mitosis (M phase).
4. Cyclin B: Active during late G2 and M phases, it partners with CDK1 to regulate the onset of mitosis by controlling the breakdown of the nuclear envelope, chromosome condensation, and spindle formation.

The activity of cyclins is tightly controlled through several mechanisms, including transcriptional regulation, protein degradation, and phosphorylation/dephosphorylation events. Dysregulation of cyclin expression or function can lead to uncontrolled cell growth and proliferation, which are hallmarks of cancer.

Cell cycle proteins are a group of regulatory proteins that control the progression of the cell cycle, which is the series of events that take place in a eukaryotic cell leading to its division and duplication. These proteins can be classified into several categories based on their functions during different stages of the cell cycle.

The major groups of cell cycle proteins include:

1. Cyclin-dependent kinases (CDKs): CDKs are serine/threonine protein kinases that regulate key transitions in the cell cycle. They require binding to a regulatory subunit called cyclin to become active. Different CDK-cyclin complexes are activated at different stages of the cell cycle.
2. Cyclins: Cyclins are a family of regulatory proteins that bind and activate CDKs. Their levels fluctuate throughout the cell cycle, with specific cyclins expressed during particular phases. For example, cyclin D is important for the G1 to S phase transition, while cyclin B is required for the G2 to M phase transition.
3. CDK inhibitors (CKIs): CKIs are regulatory proteins that bind to and inhibit CDKs, thereby preventing their activation. CKIs can be divided into two main families: the INK4 family and the Cip/Kip family. INK4 family members specifically inhibit CDK4 and CDK6, while Cip/Kip family members inhibit a broader range of CDKs.
4. Anaphase-promoting complex/cyclosome (APC/C): APC/C is an E3 ubiquitin ligase that targets specific proteins for degradation by the 26S proteasome. During the cell cycle, APC/C regulates the metaphase to anaphase transition and the exit from mitosis by targeting securin and cyclin B for degradation.
5. Other regulatory proteins: Several other proteins play crucial roles in regulating the cell cycle, such as p53, a transcription factor that responds to DNA damage and arrests the cell cycle, and the polo-like kinases (PLKs), which are involved in various aspects of mitosis.

Overall, cell cycle proteins work together to ensure the proper progression of the cell cycle, maintain genomic stability, and prevent uncontrolled cell growth, which can lead to cancer.

Cyclin-Dependent Kinase Inhibitor p16, also known as CDKN2A or INK4a, is a protein that regulates the cell cycle. It functions as an inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, which are enzymes that play a crucial role in regulating the progression of the cell cycle.

The p16 protein is produced in response to various signals, including DNA damage and oncogene activation, and its main function is to prevent the phosphorylation and activation of the retinoblastoma protein (pRb) by CDK4/6. When pRb is not phosphorylated, it binds to and inhibits the E2F transcription factor, which results in the suppression of genes required for cell cycle progression.

Therefore, p16 acts as a tumor suppressor protein by preventing the uncontrolled proliferation of cells that can lead to cancer. Mutations or deletions in the CDKN2A gene, which encodes the p16 protein, have been found in many types of human cancers, including lung, breast, and head and neck cancers.

The cell cycle is a series of events that take place in a cell leading to its division and duplication. It consists of four main phases: G1 phase, S phase, G2 phase, and M phase.

During the G1 phase, the cell grows in size and synthesizes mRNA and proteins in preparation for DNA replication. In the S phase, the cell's DNA is copied, resulting in two complete sets of chromosomes. During the G2 phase, the cell continues to grow and produces more proteins and organelles necessary for cell division.

The M phase is the final stage of the cell cycle and consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division). Mitosis results in two genetically identical daughter nuclei, while cytokinesis divides the cytoplasm and creates two separate daughter cells.

The cell cycle is regulated by various checkpoints that ensure the proper completion of each phase before progressing to the next. These checkpoints help prevent errors in DNA replication and division, which can lead to mutations and cancer.

Tumor suppressor proteins are a type of regulatory protein that helps control the cell cycle and prevent cells from dividing and growing in an uncontrolled manner. They work to inhibit tumor growth by preventing the formation of tumors or slowing down their progression. These proteins can repair damaged DNA, regulate gene expression, and initiate programmed cell death (apoptosis) if the damage is too severe for repair.

Mutations in tumor suppressor genes, which provide the code for these proteins, can lead to a decrease or loss of function in the resulting protein. This can result in uncontrolled cell growth and division, leading to the formation of tumors and cancer. Examples of tumor suppressor proteins include p53, Rb (retinoblastoma), and BRCA1/2.

Medical Definition:
Microtubule-associated proteins (MAPs) are a diverse group of proteins that bind to microtubules, which are key components of the cytoskeleton in eukaryotic cells. MAPs play crucial roles in regulating microtubule dynamics and stability, as well as in mediating interactions between microtubules and other cellular structures. They can be classified into several categories based on their functions, including:

1. Microtubule stabilizers: These MAPs promote the assembly of microtubules and protect them from disassembly by enhancing their stability. Examples include tau proteins and MAP2.
2. Microtubule dynamics regulators: These MAPs modulate the rate of microtubule polymerization and depolymerization, allowing for dynamic reorganization of the cytoskeleton during cell division and other processes. Examples include stathmin and XMAP215.
3. Microtubule motor proteins: These MAPs use energy from ATP hydrolysis to move along microtubules, transporting various cargoes within the cell. Examples include kinesin and dynein.
4. Adapter proteins: These MAPs facilitate interactions between microtubules and other cellular structures, such as membranes, organelles, or signaling molecules. Examples include MAP4 and CLASPs.

Dysregulation of MAPs has been implicated in several diseases, including neurodegenerative disorders like Alzheimer's disease (where tau proteins form abnormal aggregates called neurofibrillary tangles) and cancer (where altered microtubule dynamics can contribute to uncontrolled cell division).

Cyclin-Dependent Kinase 2 (CDK2) is a type of enzyme that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. CDK2 is activated when it binds to a regulatory subunit called a cyclin.

During the cell cycle, CDK2 helps to control the progression from the G1 phase to the S phase, where DNA replication occurs. Specifically, CDK2 phosphorylates various target proteins that are involved in the regulation of DNA replication and the initiation of mitosis, which is the process of cell division.

CDK2 activity is tightly regulated through a variety of mechanisms, including phosphorylation, dephosphorylation, and protein degradation. Dysregulation of CDK2 activity has been implicated in various human diseases, including cancer. Therefore, CDK2 is an important target for the development of therapies aimed at treating these diseases.

Cyclin D1 is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells divide and grow. Specifically, Cyclin D1 is involved in the transition from the G1 phase to the S phase of the cell cycle. It does this by forming a complex with and acting as a regulatory subunit of cyclin-dependent kinase 4 (CDK4) or CDK6, which phosphorylates and inactivates the retinoblastoma protein (pRb). This allows the E2F transcription factors to be released and activate the transcription of genes required for DNA replication and cell cycle progression.

Overexpression of Cyclin D1 has been implicated in the development of various types of cancer, as it can lead to uncontrolled cell growth and division. Therefore, Cyclin D1 is an important target for cancer therapy, and inhibitors of CDK4/6 have been developed to treat certain types of cancer that overexpress Cyclin D1.

Cyclin A is a type of cyclin protein that regulates the progression of the cell cycle, particularly through the G1 and S phases. It forms a complex with and acts as a regulatory subunit for cyclin-dependent kinases (CDKs), specifically CDK2 and CDK1. The activation of Cyclin A-CDK complexes leads to phosphorylation of various target proteins, which in turn regulates DNA replication and the transition to mitosis.

Cyclin A levels rise during the late G1 phase and peak during the S phase, after which they decline rapidly during the G2 phase. Any abnormalities in Cyclin A regulation or expression can contribute to uncontrolled cell growth and cancer development.

Cyclin E is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, particularly during the G1 phase and the transition to the S phase. It functions as a regulatory subunit of the Cyclin-dependent kinase 2 (CDK2) complex, which is responsible for promoting the progression of the cell cycle.

Cyclin E is synthesized during the late G1 phase of the cell cycle and accumulates to high levels until it forms a complex with CDK2. The Cyclin E-CDK2 complex then phosphorylates several target proteins, leading to the activation of various downstream pathways that promote DNA replication and cell cycle progression.

The regulation of Cyclin E expression and activity is tightly controlled through multiple mechanisms, including transcriptional regulation, protein stability, and proteasomal degradation. Dysregulation of Cyclin E has been implicated in various human cancers, including breast, ovarian, and lung cancer, due to its role in promoting uncontrolled cell proliferation and genomic instability.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

Cyclin-Dependent Kinase 4 (CDK4) is a type of enzyme, specifically a serine/threonine protein kinase, that plays a crucial role in the regulation of the cell cycle. The cell cycle is the series of events that take place in a cell leading to its division and duplication. CDK4, when activated by binding to cyclin D, helps to promote the transition from the G1 phase to the S phase of the cell cycle. This transition is a critical point in the regulation of cell growth and division, and dysregulation of this process can lead to uncontrolled cell growth and cancer. CDK4 inhibitors are used in the treatment of certain types of cancer, such as breast and lung cancer, to block the activity of CDK4 and prevent tumor cell proliferation.

CDC2 and CDC28 are members of the Serine/Threonine protein kinase family, which play crucial roles in the regulation of the cell cycle. These kinases were originally identified in yeast (CDC28) and humans (CDC2), but they are highly conserved across eukaryotes.

CDC2-CDC28 Kinases function as a part of larger complexes, often associated with cyclins, to control different phases of the cell cycle by phosphorylating specific substrates at key regulatory points. The activity of CDC2-CDC28 Kinases is tightly regulated through various mechanisms, including phosphorylation, dephosphorylation, and protein binding interactions.

During the G2 phase of the cell cycle, CDC2-CDC28 Kinases are inactivated by phosphorylation at specific residues (Tyr15 and Thr14). As the cell approaches mitosis, a family of phosphatases called Cdc25 removes these inhibitory phosphates, leading to activation of the kinase. Activated CDC2-CDC28 Kinases then initiate mitotic processes such as chromosome condensation and nuclear envelope breakdown.

In summary, CDC2-CDC28 Kinases are essential regulators of the eukaryotic cell cycle, controlling various aspects of cell division through phosphorylation of specific substrates. Their activity is tightly regulated to ensure proper progression through the cell cycle and prevent uncontrolled cell growth, which can lead to diseases such as cancer.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

Cyclin-dependent kinase inhibitor p57, also known as CDKN1C or p57KIP2, is a protein that regulates the cell cycle and acts as a tumor suppressor. It inhibits the activity of cyclin-dependent kinases (CDKs), which are enzymes that play crucial roles in regulating the cell cycle and transitioning from one phase to another.

The p57 protein is encoded by the CDKN1C gene, which is located on chromosome 11p15.5. This region is known as an imprinted gene cluster, meaning that only one copy of the gene is active, depending on whether it is inherited from the mother or father. In the case of p57, the paternal allele is usually silenced, and only the maternal allele is expressed.

Mutations in the CDKN1C gene can lead to several developmental disorders, including Beckwith-Wiedemann syndrome (BWS), a condition characterized by overgrowth, abdominal wall defects, and an increased risk of childhood tumors. Loss of function mutations in CDKN1C have also been associated with an increased risk of cancer, particularly Wilms' tumor, a type of kidney cancer that typically affects children.

In summary, cyclin-dependent kinase inhibitor p57 is a protein that regulates the cell cycle and acts as a tumor suppressor by inhibiting the activity of CDKs. Mutations in the CDKN1C gene can lead to developmental disorders and an increased risk of cancer.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

The G1 phase, or Gap 1 phase, is the first phase of the cell cycle, during which the cell grows in size and synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. During this phase, the cell also checks its growth and makes sure that it is large enough to proceed through the cell cycle. If the cell is not large enough, it will arrest in the G1 phase until it has grown sufficiently. The G1 phase is followed by the S phase, during which DNA replication occurs.

Cyclin-Dependent Kinase 5 (CDK5) is a type of protein kinase that plays crucial roles in the regulation of various cellular processes, particularly in neurons. Unlike other cyclin-dependent kinases, CDK5 is activated by associating with regulatory subunits called cyclins, specifically cyclin I and cyclin D1, but not during the cell cycle.

CDK5 activity is primarily involved in the development and functioning of the nervous system, where it regulates neuronal migration, differentiation, and synaptic plasticity. It has been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and various neurodevelopmental conditions.

CDK5 activity is tightly regulated by phosphorylation and interacting partners. Dysregulation of CDK5 can lead to abnormal neuronal function and contribute to the pathogenesis of neurological disorders.

Cyclin B is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. Cyclin B binds and activates cyclin-dependent kinase 1 (CDK1), forming the complex known as M-phase promoting factor (MPF). This complex triggers the events leading to cell division, such as chromosome condensation, nuclear envelope breakdown, and spindle formation. The levels of cyclin B increase during the G2 phase and are degraded by the anaphase-promoting complex/cyclosome (APC/C) at the onset of anaphase, allowing the cell cycle to progress into the next phase.

Cyclin D is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. Specifically, Cyclin D is involved in the G1 phase of the cell cycle and works in conjunction with its partner enzyme, cyclin-dependent kinase 4 (CDK4) or CDK6, to phosphorylate and regulate the activity of several key proteins that control the transition from G1 to S phase.

There are several different types of Cyclin D proteins, including Cyclin D1, Cyclin D2, and Cyclin D3, which are encoded by different genes but share similar structures and functions. Overexpression or dysregulation of Cyclin D has been implicated in the development of various human cancers, as it can lead to uncontrolled cell growth and division. Therefore, understanding the role of Cyclin D in the cell cycle and its regulation is important for developing potential cancer therapies.

CDC2 protein kinase, also known as cell division cycle 2 or CDK1, is a type of enzyme that plays a crucial role in the regulation of the cell cycle. The cell cycle is the series of events that cells undergo as they grow, replicate their DNA, and divide into two daughter cells.

CDC2 protein kinase is a member of the cyclin-dependent kinase (CDK) family, which are serine/threonine protein kinases that are activated by binding to regulatory subunits called cyclins. CDC2 protein kinase is primarily associated with the regulation of the G2 phase and the entry into mitosis, the stage of the cell cycle where nuclear and cytoplasmic division occur.

CDC2 protein kinase functions by phosphorylating various target proteins, which alters their activity and contributes to the coordination of the different events that occur during the cell cycle. The activity of CDC2 protein kinase is tightly regulated through a variety of mechanisms, including phosphorylation and dephosphorylation, as well as the binding and destruction of cyclin subunits.

Dysregulation of CDC2 protein kinase has been implicated in various human diseases, including cancer, where uncontrolled cell division can lead to the formation of tumors. Therefore, understanding the regulation and function of CDC2 protein kinase is an important area of research in molecular biology and medicine.

Cyclin-dependent kinase inhibitor proteins (CDKIs) are a family of regulatory proteins that play a crucial role in the control of the cell cycle. They function by binding to and inhibiting the activity of cyclin-dependent kinases (CDKs), which are serine/threonine protein kinases that help drive the progression of the cell cycle.

There are two main families of CDKIs: the Ink4 family and the Cip/Kip family. The Ink4 family members, including p16INK4a, p15INK4b, p18INK4c, and p19INK4d, specifically inhibit CDK4 and CDK6, preventing their association with cyclin D and thus blocking the transition from G1 to S phase of the cell cycle. The Cip/Kip family members, including p21CIP1, p27KIP1, and p57KIP2, inhibit a broader range of CDKs, including CDK1, CDK2, CDK4, and CDK6, and can regulate multiple stages of the cell cycle.

CDKIs play important roles in various biological processes, such as cell growth, differentiation, and apoptosis. Dysregulation of CDKI function has been implicated in several human diseases, including cancer, where loss or mutation of CDKIs can lead to uncontrolled cell proliferation and tumorigenesis. Therefore, CDKIs are attractive targets for the development of anti-cancer therapies.

Cyclin C is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. Specifically, Cyclin C is involved in the transition from the G1 phase to the S phase of the cell cycle, during which DNA replication occurs.

Cyclin C forms a complex with cyclin-dependent kinase 8 (CDK8) and other regulatory subunits to form the CDK8 module, which is part of the mediator complex that regulates gene transcription. The activity of Cyclin C/CDK8 is regulated by various mechanisms, including phosphorylation and degradation, to ensure proper control of the cell cycle and prevent uncontrolled cell growth and division.

Mutations in the gene encoding Cyclin C have been associated with certain types of cancer, highlighting its importance in maintaining genomic stability and preventing tumorigenesis.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Cyclin D3 is a type of cyclin protein that regulates the cell cycle, particularly during the G1 phase. It forms a complex with and acts as a regulatory subunit of CDK4 or CDK6, which are cyclin-dependent kinases. This complex plays a crucial role in phosphorylating and inactivating the retinoblastoma protein (pRb), leading to the release of E2F transcription factors that promote the expression of genes required for DNA replication and cell cycle progression into the S phase.

Cyclin D3 is primarily expressed in activated lymphocytes and is essential for normal immune function, as well as in certain tissues during development. Alterations in CYCLIN D3 gene expression or function have been implicated in several types of cancer, such as leukemias and lymphomas, due to their role in uncontrolled cell proliferation.

Retinoblastoma Protein (pRb or RB1) is a tumor suppressor protein that plays a critical role in regulating the cell cycle and preventing uncontrolled cell growth. It is encoded by the RB1 gene, located on chromosome 13. The retinoblastoma protein functions as a regulatory checkpoint in the cell cycle, preventing cells from progressing into the S phase (DNA synthesis phase) until certain conditions are met.

When pRb is in its active state, it binds to and inhibits the activity of E2F transcription factors, which promote the expression of genes required for DNA replication and cell cycle progression. Phosphorylation of pRb by cyclin-dependent kinases (CDKs) leads to the release of E2F factors, allowing them to activate their target genes and drive the cell into S phase.

Mutations in the RB1 gene can result in the production of a nonfunctional or reduced amount of pRb protein, leading to uncontrolled cell growth and an increased risk of developing retinoblastoma, a rare form of eye cancer, as well as other types of tumors.

Cyclin-Dependent Kinase 6 (CDK6) is a type of enzyme known as a protein kinase, which adds phosphate groups to other proteins in the cell. CDK6 is primarily involved in regulating the cell cycle, the process by which cells divide and grow.

CDK6 functions by binding to cyclin proteins, forming active complexes that help drive the progression of the cell cycle from one phase to the next. Specifically, CDK6 plays a crucial role in the transition from the G1 phase to the S phase of the cell cycle, where DNA replication occurs.

CDK6 activity is tightly regulated by various mechanisms, including phosphorylation and dephosphorylation, as well as by binding to inhibitory proteins such as p16INK4a and p21CIP1. Dysregulation of CDK6 has been implicated in the development of several types of cancer, making it a potential target for cancer therapy.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

In the context of cell biology, "S phase" refers to the part of the cell cycle during which DNA replication occurs. The "S" stands for synthesis, reflecting the active DNA synthesis that takes place during this phase. It is preceded by G1 phase (gap 1) and followed by G2 phase (gap 2), with mitosis (M phase) being the final stage of the cell cycle.

During S phase, the cell's DNA content effectively doubles as each chromosome is replicated to ensure that the two resulting daughter cells will have the same genetic material as the parent cell. This process is carefully regulated and coordinated with other events in the cell cycle to maintain genomic stability.

Cyclin B1 is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 1 (CDK1), also known as CDC2. During the G2 phase, Cyclin B1 levels accumulate and upon reaching a certain threshold, it binds to CDK1 to form the maturation promoting factor (MPF). The activation of MPF triggers the onset of mitosis by promoting nuclear envelope breakdown, chromosome condensation, and other events required for cell division. After the completion of mitosis, Cyclin B1 is degraded by the ubiquitin-proteasome system, allowing the cell cycle to progress back into G1 phase.

Cyclin-Dependent Kinase Inhibitor p18, also known as CDKN2C or INK4c, is a protein that regulates the cell cycle. It inhibits the activity of cyclin-dependent kinases (CDKs), specifically the CDK4 and CDK6 proteins, which play crucial roles in regulating the progression of the cell cycle.

The p18 protein functions as a tumor suppressor by preventing the phosphorylation and activation of the retinoblastoma protein (pRb) by CDK4/6. When pRb is not phosphorylated, it remains bound to E2F transcription factors, inhibiting their ability to promote the expression of genes required for cell cycle progression.

Mutations or deletions in the CDKN2C gene can lead to uncontrolled cell growth and contribute to tumor development, making p18 an important factor in cancer biology and potential therapeutic target.

Tumor suppressor protein p53, also known as p53 or tumor protein p53, is a nuclear phosphoprotein that plays a crucial role in preventing cancer development and maintaining genomic stability. It does so by regulating the cell cycle and acting as a transcription factor for various genes involved in apoptosis (programmed cell death), DNA repair, and cell senescence (permanent cell growth arrest).

In response to cellular stress, such as DNA damage or oncogene activation, p53 becomes activated and accumulates in the nucleus. Activated p53 can then bind to specific DNA sequences and promote the transcription of target genes that help prevent the proliferation of potentially cancerous cells. These targets include genes involved in cell cycle arrest (e.g., CDKN1A/p21), apoptosis (e.g., BAX, PUMA), and DNA repair (e.g., GADD45).

Mutations in the TP53 gene, which encodes p53, are among the most common genetic alterations found in human cancers. These mutations often lead to a loss or reduction of p53's tumor suppressive functions, allowing cancer cells to proliferate uncontrollably and evade apoptosis. As a result, p53 has been referred to as "the guardian of the genome" due to its essential role in preventing tumorigenesis.

Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.

When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.

Examples of proto-oncogene proteins include:

1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.

Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Cyclin D2 is a type of cyclin protein that regulates the cell cycle, particularly in the G1 phase. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 4 (CDK4) or CDK6, promoting the transition from G1 to S phase of the cell cycle. The expression of cyclin D2 is regulated by various growth factors, hormones, and oncogenes, and its dysregulation has been implicated in the development of several types of cancer.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

E2F1 is a member of the E2F family of transcription factors, which are involved in the regulation of cell cycle progression and apoptosis (programmed cell death). Specifically, E2F1 plays a role as a transcriptional activator, binding to specific DNA sequences and promoting the expression of genes required for the G1/S transition of the cell cycle.

In more detail, E2F1 forms a complex with a retinoblastoma protein (pRb) in the G0 and early G1 phases of the cell cycle. When pRb is phosphorylated by cyclin-dependent kinases during the late G1 phase, E2F1 is released and can then bind to its target DNA sequences and activate transcription of genes involved in DNA replication and cell cycle progression.

However, if E2F1 is overexpressed or activated inappropriately, it can also promote apoptosis, making it a key player in both cell proliferation and cell death pathways. Dysregulation of E2F1 has been implicated in the development of various human cancers, including breast, lung, and prostate cancer.

Cyclin A1 is a type of cyclin protein that regulates the cell cycle, particularly during the S and G2 phases. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 2 (CDK2), helping to control the transition from the G1 phase to the S phase and from the S phase to the G2 phase. Cyclin A1 is expressed in various tissues, including ovary, testis, bone marrow, and lymphoid cells. Overexpression or dysregulation of cyclin A1 has been implicated in several types of cancer, making it a potential target for cancer therapy.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Purines are heterocyclic aromatic organic compounds that consist of a pyrimidine ring fused to an imidazole ring. They are fundamental components of nucleotides, which are the building blocks of DNA and RNA. In the body, purines can be synthesized endogenously or obtained through dietary sources such as meat, seafood, and certain vegetables.

Once purines are metabolized, they are broken down into uric acid, which is excreted by the kidneys. Elevated levels of uric acid in the body can lead to the formation of uric acid crystals, resulting in conditions such as gout or kidney stones. Therefore, maintaining a balanced intake of purine-rich foods and ensuring proper kidney function are essential for overall health.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Mitosis is a type of cell division in which the genetic material of a single cell, called the mother cell, is equally distributed into two identical daughter cells. It's a fundamental process that occurs in multicellular organisms for growth, maintenance, and repair, as well as in unicellular organisms for reproduction.

The process of mitosis can be broken down into several stages: prophase, prometaphase, metaphase, anaphase, and telophase. During prophase, the chromosomes condense and become visible, and the nuclear envelope breaks down. In prometaphase, the nuclear membrane is completely disassembled, and the mitotic spindle fibers attach to the chromosomes at their centromeres.

During metaphase, the chromosomes align at the metaphase plate, an imaginary line equidistant from the two spindle poles. In anaphase, sister chromatids are pulled apart by the spindle fibers and move toward opposite poles of the cell. Finally, in telophase, new nuclear envelopes form around each set of chromosomes, and the chromosomes decondense and become less visible.

Mitosis is followed by cytokinesis, a process that divides the cytoplasm of the mother cell into two separate daughter cells. The result of mitosis and cytokinesis is two genetically identical cells, each with the same number and kind of chromosomes as the original parent cell.

Cyclin G is a type of protein that belongs to the cyclin family, which are involved in the regulation of the cell cycle. The human Cyclin G gene encodes two isoforms, Cyclin G1 and Cyclin G2, which share a similar structure but have different functions.

Cyclin G1 is known to play a role in the negative regulation of the cell cycle, particularly during the G1 phase. It interacts with several proteins, including CDKs (cyclin-dependent kinases), to regulate the activity of various transcription factors and other signaling pathways that control cell growth and division.

Cyclin G2, on the other hand, has been implicated in the regulation of DNA damage response and apoptosis (programmed cell death). It interacts with CDKs and other proteins to modulate the activity of various signaling pathways involved in these processes.

Overall, Cyclin G plays important roles in regulating cell cycle progression, DNA damage response, and apoptosis, and its dysregulation has been linked to several human diseases, including cancer.

The G2 phase, also known as the "gap 2 phase," is a stage in the cell cycle that occurs after DNA replication (S phase) and before cell division (mitosis). During this phase, the cell prepares for mitosis by completing the synthesis of proteins and organelles needed for chromosome separation. The cell also checks for any errors or damage to the DNA before entering mitosis. This phase is a critical point in the cell cycle where proper regulation ensures the faithful transmission of genetic information from one generation of cells to the next. If significant DNA damage is detected during G2, the cell may undergo programmed cell death (apoptosis) instead of dividing.

Transcription factor DP1 (TFDP1) is not a specific medical term, but it is a term used in molecular biology and genetics. TFDP1 is a protein that functions as a transcription factor, which means it helps regulate the expression of genes by binding to specific DNA sequences and controlling the rate of transcription of those genes into messenger RNA (mRNA).

TFDP1 typically forms a complex with another transcription factor called E2F, and this complex plays a critical role in regulating the cell cycle and promoting cell division. TFDP1 can act as both a transcriptional activator and repressor, depending on which E2F family member it binds to and the specific context of the cell.

Mutations or dysregulation of TFDP1 have been implicated in various human diseases, including cancer. For example, overexpression of TFDP1 has been observed in several types of cancer, such as breast, lung, and prostate cancer, and is often associated with poor clinical outcomes. Therefore, understanding the role of TFDP1 in gene regulation and cellular processes may provide insights into the development of new therapeutic strategies for treating human diseases.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Proliferating Cell Nuclear Antigen (PCNA) is a protein that plays an essential role in the process of DNA replication and repair in eukaryotic cells. It functions as a cofactor for DNA polymerase delta, enhancing its activity during DNA synthesis. PCNA forms a sliding clamp around DNA, allowing it to move along the template and coordinate the actions of various enzymes involved in DNA metabolism.

PCNA is often used as a marker for cell proliferation because its levels increase in cells that are actively dividing or have been stimulated to enter the cell cycle. Immunostaining techniques can be used to detect PCNA and determine the proliferative status of tissues or cultures. In this context, 'proliferating' refers to the rapid multiplication of cells through cell division.

Cyclin-Dependent Kinase Inhibitor p15, also known as CDKN2B or INK4b, is a protein that regulates the cell cycle. It inhibits the activity of cyclin-dependent kinases (CDKs), specifically the CDK4 and CDK6 complexes with cyclin D, which play a crucial role in regulating the progression of the cell cycle from the G1 phase to the S phase.

The p15 protein is encoded by the CDKN2B gene, which is located on human chromosome 9p21. The expression of the CDKN2B gene is induced by various signals, including DNA damage and differentiation signals, leading to the inhibition of CDK4/6-cyclin D complexes and cell cycle arrest in the G1 phase. This provides an essential mechanism for preventing cells with damaged DNA from entering the S phase and undergoing DNA replication, thereby ensuring genomic stability and preventing tumorigenesis.

Mutations or deletions of the CDKN2B gene have been implicated in various human cancers, including gliomas, melanomas, and leukemias, suggesting that the loss of p15 function may contribute to tumor development and progression.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Cyclin G1 is a type of protein that belongs to the cyclin family, which are involved in the regulation of the cell cycle. The cell cycle is the series of events that take place as a cell grows, copies its DNA, and divides into two daughter cells.

Cyclin G1 regulates the cell cycle by interacting with various cyclin-dependent kinases (CDKs), which are enzymes that help control the progression of the cell cycle. Specifically, Cyclin G1 has been shown to inhibit the activity of CDK1 and CDK2, which play important roles in regulating the transition from the G1 phase to the S phase of the cell cycle.

Cyclin G1 has also been implicated in other cellular processes, including DNA damage repair, apoptosis (programmed cell death), and tumor suppression. Dysregulation of Cyclin G1 has been linked to various types of cancer, making it a potential target for cancer therapy.

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

Cyclin A2 is a type of cyclin protein that regulates the cell cycle, which is the series of events that cells undergo as they grow and divide. Specifically, Cyclin A2 plays a role in the progression from the G1 phase to the S phase (DNA synthesis phase) and from the G2 phase to the M phase (mitosis phase) of the cell cycle. It does this by binding to and activating cyclin-dependent kinases (CDKs), which are enzymes that help regulate the cell cycle.

Cyclin A2 is expressed at various points during the cell cycle, but its levels peak during the S and G2 phases. The protein is degraded during mitosis, ensuring that it is not present in excess during the next cell cycle. Dysregulation of Cyclin A2 has been implicated in the development of cancer, as uncontrolled cell growth and division are hallmarks of this disease.

E2F transcription factors are a family of proteins that play crucial roles in the regulation of the cell cycle, DNA repair, and apoptosis (programmed cell death). These factors bind to specific DNA sequences called E2F responsive elements, located in the promoter regions of target genes. They can act as either transcriptional activators or repressors, depending on which E2F family member is involved, the presence of co-factors, and the phase of the cell cycle.

The E2F family consists of eight members, divided into two groups based on their functions: activator E2Fs (E2F1, E2F2, and E2F3a) and repressor E2Fs (E2F3b, E2F4, E2F5, E2F6, and E2F7). Activator E2Fs promote the expression of genes required for cell cycle progression, DNA replication, and repair. Repressor E2Fs, on the other hand, inhibit the transcription of these same genes as well as genes involved in differentiation and apoptosis.

Dysregulation of E2F transcription factors has been implicated in various human diseases, including cancer. Overexpression or hyperactivation of activator E2Fs can lead to uncontrolled cell proliferation and tumorigenesis, while loss of function or inhibition of repressor E2Fs can result in impaired differentiation and increased susceptibility to malignancies. Therefore, understanding the roles and regulation of E2F transcription factors is essential for developing novel therapeutic strategies against cancer and other diseases associated with cell cycle dysregulation.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

Cyclin-Dependent Kinase Inhibitor p19, also known as CDKN2A or INK4a, is a protein that functions as a tumor suppressor. It inhibits the activity of cyclin-dependent kinases (CDKs), which are enzymes that play crucial roles in regulating the cell cycle.

The cell cycle is a series of events that cells undergo as they grow and divide. CDKs help to control the progression of the cell cycle by phosphorylating various target proteins, including other CDKs and proteins involved in DNA replication and mitosis.

Cyclin-Dependent Kinase Inhibitor p19 inhibits CDK4 and CDK6, which are important regulators of the G1 phase of the cell cycle. By inhibiting these kinases, p19 helps to prevent the premature entry of cells into the S phase of the cell cycle, where DNA replication occurs.

Mutations in the gene that encodes Cyclin-Dependent Kinase Inhibitor p19 have been associated with several types of cancer, including melanoma, pancreatic cancer, and lung cancer. These mutations can lead to the loss or reduction of p19 function, which can contribute to uncontrolled cell growth and tumor formation.

S-phase kinase-associated proteins (Skp2) are a group of proteins that are associated with the S-phase kinase, which is a type of enzyme that helps to regulate the cell cycle. Specifically, Skp2 is involved in the ubiquitination and degradation of certain proteins that play a role in controlling the progression of the cell cycle.

Skp2 is a member of the F-box protein family, which are components of the Skp1-Cul1-F-box (SCF) complex, a type of E3 ubiquitin ligase. The SCF complex recognizes and binds to specific proteins, tagging them for ubiquitination and subsequent degradation by the proteasome.

One of the key targets of Skp2 is the tumor suppressor protein p27, which inhibits the activity of cyclin-dependent kinases (CDKs) and helps to regulate the transition from the G1 phase to the S phase of the cell cycle. By targeting p27 for degradation, Skp2 promotes the progression of the cell cycle and has been implicated in the development of various types of cancer.

Overall, Skp2 plays a critical role in regulating the cell cycle and has important implications for the development and treatment of various diseases, including cancer.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Down-regulation is a process that occurs in response to various stimuli, where the number or sensitivity of cell surface receptors or the expression of specific genes is decreased. This process helps maintain homeostasis within cells and tissues by reducing the ability of cells to respond to certain signals or molecules.

In the context of cell surface receptors, down-regulation can occur through several mechanisms:

1. Receptor internalization: After binding to their ligands, receptors can be internalized into the cell through endocytosis. Once inside the cell, these receptors may be degraded or recycled back to the cell surface in smaller numbers.
2. Reduced receptor synthesis: Down-regulation can also occur at the transcriptional level, where the expression of genes encoding for specific receptors is decreased, leading to fewer receptors being produced.
3. Receptor desensitization: Prolonged exposure to a ligand can lead to a decrease in receptor sensitivity or affinity, making it more difficult for the cell to respond to the signal.

In the context of gene expression, down-regulation refers to the decreased transcription and/or stability of specific mRNAs, leading to reduced protein levels. This process can be induced by various factors, including microRNA (miRNA)-mediated regulation, histone modification, or DNA methylation.

Down-regulation is an essential mechanism in many physiological processes and can also contribute to the development of several diseases, such as cancer and neurodegenerative disorders.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

Intracellular signaling peptides and proteins are molecules that play a crucial role in transmitting signals within cells, which ultimately lead to changes in cell behavior or function. These signals can originate from outside the cell (extracellular) or within the cell itself. Intracellular signaling molecules include various types of peptides and proteins, such as:

1. G-protein coupled receptors (GPCRs): These are seven-transmembrane domain receptors that bind to extracellular signaling molecules like hormones, neurotransmitters, or chemokines. Upon activation, they initiate a cascade of intracellular signals through G proteins and secondary messengers.
2. Receptor tyrosine kinases (RTKs): These are transmembrane receptors that bind to growth factors, cytokines, or hormones. Activation of RTKs leads to autophosphorylation of specific tyrosine residues, creating binding sites for intracellular signaling proteins such as adapter proteins, phosphatases, and enzymes like Ras, PI3K, and Src family kinases.
3. Second messenger systems: Intracellular second messengers are small molecules that amplify and propagate signals within the cell. Examples include cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), diacylglycerol (DAG), inositol triphosphate (IP3), calcium ions (Ca2+), and nitric oxide (NO). These second messengers activate or inhibit various downstream effectors, leading to changes in cellular responses.
4. Signal transduction cascades: Intracellular signaling proteins often form complex networks of interacting molecules that relay signals from the plasma membrane to the nucleus. These cascades involve kinases (protein kinases A, B, C, etc.), phosphatases, and adapter proteins, which ultimately regulate gene expression, cell cycle progression, metabolism, and other cellular processes.
5. Ubiquitination and proteasome degradation: Intracellular signaling pathways can also control protein stability by modulating ubiquitin-proteasome degradation. E3 ubiquitin ligases recognize specific substrates and conjugate them with ubiquitin molecules, targeting them for proteasomal degradation. This process regulates the abundance of key signaling proteins and contributes to signal termination or amplification.

In summary, intracellular signaling pathways involve a complex network of interacting proteins that relay signals from the plasma membrane to various cellular compartments, ultimately regulating gene expression, metabolism, and other cellular processes. Dysregulation of these pathways can contribute to disease development and progression, making them attractive targets for therapeutic intervention.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

p38 Mitogen-Activated Protein Kinases (p38 MAPKs) are a family of conserved serine-threonine protein kinases that play crucial roles in various cellular processes, including inflammation, immune response, differentiation, apoptosis, and stress responses. They are activated by diverse stimuli such as cytokines, ultraviolet radiation, heat shock, osmotic stress, and lipopolysaccharides (LPS).

Once activated, p38 MAPKs phosphorylate and regulate several downstream targets, including transcription factors and other protein kinases. This regulation leads to the expression of genes involved in inflammation, cell cycle arrest, and apoptosis. Dysregulation of p38 MAPK signaling has been implicated in various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, p38 MAPKs are considered promising targets for developing new therapeutic strategies to treat these conditions.

3T3 cells are a type of cell line that is commonly used in scientific research. The name "3T3" is derived from the fact that these cells were developed by treating mouse embryo cells with a chemical called trypsin and then culturing them in a flask at a temperature of 37 degrees Celsius.

Specifically, 3T3 cells are a type of fibroblast, which is a type of cell that is responsible for producing connective tissue in the body. They are often used in studies involving cell growth and proliferation, as well as in toxicity tests and drug screening assays.

One particularly well-known use of 3T3 cells is in the 3T3-L1 cell line, which is a subtype of 3T3 cells that can be differentiated into adipocytes (fat cells) under certain conditions. These cells are often used in studies of adipose tissue biology and obesity.

It's important to note that because 3T3 cells are a type of immortalized cell line, they do not always behave exactly the same way as primary cells (cells that are taken directly from a living organism). As such, researchers must be careful when interpreting results obtained using 3T3 cells and consider any potential limitations or artifacts that may arise due to their use.

Mitogen-Activated Protein Kinases (MAPKs) are a family of serine/threonine protein kinases that play crucial roles in various cellular processes, including proliferation, differentiation, transformation, and apoptosis, in response to diverse stimuli such as mitogens, growth factors, hormones, cytokines, and environmental stresses. They are highly conserved across eukaryotes and consist of a three-tiered kinase module composed of MAPK kinase kinases (MAP3Ks), MAPK kinases (MKKs or MAP2Ks), and MAPKs.

Activation of MAPKs occurs through a sequential phosphorylation and activation cascade, where MAP3Ks phosphorylate and activate MKKs, which in turn phosphorylate and activate MAPKs at specific residues (Thr-X-Tyr or Ser-Pro motifs). Once activated, MAPKs can further phosphorylate and regulate various downstream targets, including transcription factors and other protein kinases.

There are four major groups of MAPKs in mammals: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5/BMK1. Each group of MAPKs has distinct upstream activators, downstream targets, and cellular functions, allowing for a high degree of specificity in signal transduction and cellular responses. Dysregulation of MAPK signaling pathways has been implicated in various human diseases, including cancer, diabetes, neurodegenerative disorders, and inflammatory diseases.

Mitogen-Activated Protein Kinase 1 (MAPK1), also known as Extracellular Signal-Regulated Kinase 2 (ERK2), is a protein kinase that plays a crucial role in intracellular signal transduction pathways. It is a member of the MAPK family, which regulates various cellular processes such as proliferation, differentiation, apoptosis, and stress response.

MAPK1 is activated by a cascade of phosphorylation events initiated by upstream activators like MAPKK (Mitogen-Activated Protein Kinase Kinase) in response to various extracellular signals such as growth factors, hormones, and mitogens. Once activated, MAPK1 phosphorylates downstream targets, including transcription factors and other protein kinases, thereby modulating their activities and ultimately influencing gene expression and cellular responses.

MAPK1 is widely expressed in various tissues and cells, and its dysregulation has been implicated in several pathological conditions, including cancer, inflammation, and neurodegenerative diseases. Therefore, understanding the regulation and function of MAPK1 signaling pathways has important implications for developing therapeutic strategies to treat these disorders.

Mitogen-Activated Protein Kinase Kinases (MAP2K or MEK) are a group of protein kinases that play a crucial role in intracellular signal transduction pathways. They are so named because they are activated by mitogens, which are substances that stimulate cell division, and other extracellular signals.

MAP2Ks are positioned upstream of the Mitogen-Activated Protein Kinases (MAPK) in a three-tiered kinase cascade. Once activated, MAP2Ks phosphorylate and activate MAPKs, which then go on to regulate various cellular processes such as proliferation, differentiation, survival, and apoptosis.

There are several subfamilies of MAP2Ks, including MEK1/2, MEK3/6 (also known as MKK3/6), MEK4/7 (also known as MKK4/7), and MEK5. Each MAP2K is specific to activating a particular MAPK, and they are activated by different MAP3Ks (MAP kinase kinase kinases) in response to various extracellular signals.

Dysregulation of the MAPK/MAP2K signaling pathways has been implicated in numerous diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, targeting these pathways with therapeutic agents has emerged as a promising strategy for treating various diseases.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

Small interfering RNA (siRNA) is a type of short, double-stranded RNA molecule that plays a role in the RNA interference (RNAi) pathway. The RNAi pathway is a natural cellular process that regulates gene expression by targeting and destroying specific messenger RNA (mRNA) molecules, thereby preventing the translation of those mRNAs into proteins.

SiRNAs are typically 20-25 base pairs in length and are generated from longer double-stranded RNA precursors called hairpin RNAs or dsRNAs by an enzyme called Dicer. Once generated, siRNAs associate with a protein complex called the RNA-induced silencing complex (RISC), which uses one strand of the siRNA (the guide strand) to recognize and bind to complementary sequences in the target mRNA. The RISC then cleaves the target mRNA, leading to its degradation and the inhibition of protein synthesis.

SiRNAs have emerged as a powerful tool for studying gene function and have shown promise as therapeutic agents for a variety of diseases, including viral infections, cancer, and genetic disorders. However, their use as therapeutics is still in the early stages of development, and there are challenges associated with delivering siRNAs to specific cells and tissues in the body.

Pyrimidines are heterocyclic aromatic organic compounds similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. They are one of the two types of nucleobases found in nucleic acids, the other being purines. The pyrimidine bases include cytosine (C) and thymine (T) in DNA, and uracil (U) in RNA, which pair with guanine (G) and adenine (A), respectively, through hydrogen bonding to form the double helix structure of nucleic acids. Pyrimidines are also found in many other biomolecules and have various roles in cellular metabolism and genetic regulation.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Cyclic AMP (cAMP)-dependent protein kinases, also known as protein kinase A (PKA), are a family of enzymes that play a crucial role in intracellular signaling pathways. These enzymes are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

PKA is composed of two regulatory subunits and two catalytic subunits. When cAMP binds to the regulatory subunits, it causes a conformational change that leads to the dissociation of the catalytic subunits. The freed catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity.

The cAMP-dependent protein kinases are activated in response to a variety of extracellular signals, such as hormones and neurotransmitters, that bind to G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). These signals lead to the activation of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The resulting increase in intracellular cAMP levels triggers the activation of PKA and the downstream phosphorylation of target proteins.

Overall, cAMP-dependent protein kinases are essential regulators of many fundamental cellular processes and play a critical role in maintaining normal physiology and homeostasis. Dysregulation of these enzymes has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Neoplastic gene expression regulation refers to the processes that control the production of proteins and other molecules from genes in neoplastic cells, or cells that are part of a tumor or cancer. In a normal cell, gene expression is tightly regulated to ensure that the right genes are turned on or off at the right time. However, in cancer cells, this regulation can be disrupted, leading to the overexpression or underexpression of certain genes.

Neoplastic gene expression regulation can be affected by a variety of factors, including genetic mutations, epigenetic changes, and signals from the tumor microenvironment. These changes can lead to the activation of oncogenes (genes that promote cancer growth and development) or the inactivation of tumor suppressor genes (genes that prevent cancer).

Understanding neoplastic gene expression regulation is important for developing new therapies for cancer, as targeting specific genes or pathways involved in this process can help to inhibit cancer growth and progression.

The cell nucleus is a membrane-bound organelle found in the eukaryotic cells (cells with a true nucleus). It contains most of the cell's genetic material, organized as DNA molecules in complex with proteins, RNA molecules, and histones to form chromosomes.

The primary function of the cell nucleus is to regulate and control the activities of the cell, including growth, metabolism, protein synthesis, and reproduction. It also plays a crucial role in the process of mitosis (cell division) by separating and protecting the genetic material during this process. The nuclear membrane, or nuclear envelope, surrounding the nucleus is composed of two lipid bilayers with numerous pores that allow for the selective transport of molecules between the nucleoplasm (nucleus interior) and the cytoplasm (cell exterior).

The cell nucleus is a vital structure in eukaryotic cells, and its dysfunction can lead to various diseases, including cancer and genetic disorders.

Mitogen-Activated Protein Kinase 3 (MAPK3), also known as extracellular signal-regulated kinase 1 (ERK1), is a serine/threonine protein kinase that plays a crucial role in intracellular signal transduction pathways. It is involved in the regulation of various cellular processes, including proliferation, differentiation, and survival, in response to extracellular stimuli such as growth factors, hormones, and stress.

MAPK3 is activated through a phosphorylation cascade that involves the activation of upstream MAPK kinases (MKK or MEK). Once activated, MAPK3 can phosphorylate and activate various downstream targets, including transcription factors, to regulate gene expression. Dysregulation of MAPK3 signaling has been implicated in several diseases, including cancer and neurological disorders.

Protein-kinase B, also known as AKT, is a group of intracellular proteins that play a crucial role in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. The AKT family includes three isoforms: AKT1, AKT2, and AKT3, which are encoded by the genes PKBalpha, PKBbeta, and PKBgamma, respectively.

Proto-oncogene proteins c-AKT refer to the normal, non-mutated forms of these proteins that are involved in the regulation of cell growth and survival under physiological conditions. However, when these genes are mutated or overexpressed, they can become oncogenes, leading to uncontrolled cell growth and cancer development.

Activation of c-AKT occurs through a signaling cascade that begins with the binding of extracellular ligands such as insulin-like growth factor 1 (IGF-1) or epidermal growth factor (EGF) to their respective receptors on the cell surface. This triggers a series of phosphorylation events that ultimately lead to the activation of c-AKT, which then phosphorylates downstream targets involved in various cellular processes.

In summary, proto-oncogene proteins c-AKT are normal intracellular proteins that play essential roles in regulating cell growth and survival under physiological conditions. However, their dysregulation can contribute to cancer development and progression.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Recombinant fusion proteins are artificially created biomolecules that combine the functional domains or properties of two or more different proteins into a single protein entity. They are generated through recombinant DNA technology, where the genes encoding the desired protein domains are linked together and expressed as a single, chimeric gene in a host organism, such as bacteria, yeast, or mammalian cells.

The resulting fusion protein retains the functional properties of its individual constituent proteins, allowing for novel applications in research, diagnostics, and therapeutics. For instance, recombinant fusion proteins can be designed to enhance protein stability, solubility, or immunogenicity, making them valuable tools for studying protein-protein interactions, developing targeted therapies, or generating vaccines against infectious diseases or cancer.

Examples of recombinant fusion proteins include:

1. Etaglunatide (ABT-523): A soluble Fc fusion protein that combines the heavy chain fragment crystallizable region (Fc) of an immunoglobulin with the extracellular domain of the human interleukin-6 receptor (IL-6R). This fusion protein functions as a decoy receptor, neutralizing IL-6 and its downstream signaling pathways in rheumatoid arthritis.
2. Etanercept (Enbrel): A soluble TNF receptor p75 Fc fusion protein that binds to tumor necrosis factor-alpha (TNF-α) and inhibits its proinflammatory activity, making it a valuable therapeutic option for treating autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, and psoriasis.
3. Abatacept (Orencia): A fusion protein consisting of the extracellular domain of cytotoxic T-lymphocyte antigen 4 (CTLA-4) linked to the Fc region of an immunoglobulin, which downregulates T-cell activation and proliferation in autoimmune diseases like rheumatoid arthritis.
4. Belimumab (Benlysta): A monoclonal antibody that targets B-lymphocyte stimulator (BLyS) protein, preventing its interaction with the B-cell surface receptor and inhibiting B-cell activation in systemic lupus erythematosus (SLE).
5. Romiplostim (Nplate): A fusion protein consisting of a thrombopoietin receptor agonist peptide linked to an immunoglobulin Fc region, which stimulates platelet production in patients with chronic immune thrombocytopenia (ITP).
6. Darbepoetin alfa (Aranesp): A hyperglycosylated erythropoiesis-stimulating protein that functions as a longer-acting form of recombinant human erythropoietin, used to treat anemia in patients with chronic kidney disease or cancer.
7. Palivizumab (Synagis): A monoclonal antibody directed against the F protein of respiratory syncytial virus (RSV), which prevents RSV infection and is administered prophylactically to high-risk infants during the RSV season.
8. Ranibizumab (Lucentis): A recombinant humanized monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor A (VEGF-A), used in the treatment of age-related macular degeneration, diabetic retinopathy, and other ocular disorders.
9. Cetuximab (Erbitux): A chimeric monoclonal antibody that binds to epidermal growth factor receptor (EGFR), used in the treatment of colorectal cancer and head and neck squamous cell carcinoma.
10. Adalimumab (Humira): A fully humanized monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
11. Bevacizumab (Avastin): A recombinant humanized monoclonal antibody that binds to VEGF-A, used in the treatment of various cancers, including colorectal, lung, breast, and kidney cancer.
12. Trastuzumab (Herceptin): A humanized monoclonal antibody that targets HER2/neu receptor, used in the treatment of breast cancer.
13. Rituximab (Rituxan): A chimeric monoclonal antibody that binds to CD20 antigen on B cells, used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis.
14. Palivizumab (Synagis): A humanized monoclonal antibody that binds to the F protein of respiratory syncytial virus, used in the prevention of respiratory syncytial virus infection in high-risk infants.
15. Infliximab (Remicade): A chimeric monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.
16. Natalizumab (Tysabri): A humanized monoclonal antibody that binds to α4β1 integrin, used in the treatment of multiple sclerosis and Crohn's disease.
17. Adalimumab (Humira): A fully human monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.
18. Golimumab (Simponi): A fully human monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.
19. Certolizumab pegol (Cimzia): A PEGylated Fab' fragment of a humanized monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.
20. Ustekinumab (Stelara): A fully human monoclonal antibody that targets IL-12 and IL-23, used in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease.
21. Secukinumab (Cosentyx): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.
22. Ixekizumab (Taltz): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis and psoriatic arthritis.
23. Brodalumab (Siliq): A fully human monoclonal antibody that targets IL-17 receptor A, used in the treatment of psoriasis.
24. Sarilumab (Kevzara): A fully human monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis.
25. Tocilizumab (Actemra): A humanized monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell-induced cytokine release syndrome.
26. Siltuximab (Sylvant): A chimeric monoclonal antibody that targets IL-6, used in the treatment of multicentric Castleman disease.
27. Satralizumab (Enspryng): A humanized monoclonal antibody that targets IL-6 receptor alpha, used in the treatment of neuromyelitis optica spectrum disorder.
28. Sirukumab (Plivensia): A human monoclonal antibody that targets IL-6, used in the treatment

Benzamides are a class of organic compounds that consist of a benzene ring (a aromatic hydrocarbon) attached to an amide functional group. The amide group can be bound to various substituents, leading to a variety of benzamide derivatives with different biological activities.

In a medical context, some benzamides have been developed as drugs for the treatment of various conditions. For example, danzol (a benzamide derivative) is used as a hormonal therapy for endometriosis and breast cancer. Additionally, other benzamides such as sulpiride and amisulpride are used as antipsychotic medications for the treatment of schizophrenia and related disorders.

It's important to note that while some benzamides have therapeutic uses, others may be toxic or have adverse effects, so they should only be used under the supervision of a medical professional.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

JNK (c-Jun N-terminal kinase) Mitogen-Activated Protein Kinases are a subgroup of the Ser/Thr protein kinases that are activated by stress stimuli and play important roles in various cellular processes, including inflammation, apoptosis, and differentiation. They are involved in the regulation of gene expression through phosphorylation of transcription factors such as c-Jun. JNKs are activated by a variety of upstream kinases, including MAP2Ks (MKK4/SEK1 and MKK7), which are in turn activated by MAP3Ks (such as ASK1, MEKK1, MLKs, and TAK1). JNK signaling pathways have been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.

Fibroblasts are specialized cells that play a critical role in the body's immune response and wound healing process. They are responsible for producing and maintaining the extracellular matrix (ECM), which is the non-cellular component present within all tissues and organs, providing structural support and biochemical signals for surrounding cells.

Fibroblasts produce various ECM proteins such as collagens, elastin, fibronectin, and laminins, forming a complex network of fibers that give tissues their strength and flexibility. They also help in the regulation of tissue homeostasis by controlling the turnover of ECM components through the process of remodeling.

In response to injury or infection, fibroblasts become activated and start to proliferate rapidly, migrating towards the site of damage. Here, they participate in the inflammatory response, releasing cytokines and chemokines that attract immune cells to the area. Additionally, they deposit new ECM components to help repair the damaged tissue and restore its functionality.

Dysregulation of fibroblast activity has been implicated in several pathological conditions, including fibrosis (excessive scarring), cancer (where they can contribute to tumor growth and progression), and autoimmune diseases (such as rheumatoid arthritis).

Biological models, also known as physiological models or organismal models, are simplified representations of biological systems, processes, or mechanisms that are used to understand and explain the underlying principles and relationships. These models can be theoretical (conceptual or mathematical) or physical (such as anatomical models, cell cultures, or animal models). They are widely used in biomedical research to study various phenomena, including disease pathophysiology, drug action, and therapeutic interventions.

Examples of biological models include:

1. Mathematical models: These use mathematical equations and formulas to describe complex biological systems or processes, such as population dynamics, metabolic pathways, or gene regulation networks. They can help predict the behavior of these systems under different conditions and test hypotheses about their underlying mechanisms.
2. Cell cultures: These are collections of cells grown in a controlled environment, typically in a laboratory dish or flask. They can be used to study cellular processes, such as signal transduction, gene expression, or metabolism, and to test the effects of drugs or other treatments on these processes.
3. Animal models: These are living organisms, usually vertebrates like mice, rats, or non-human primates, that are used to study various aspects of human biology and disease. They can provide valuable insights into the pathophysiology of diseases, the mechanisms of drug action, and the safety and efficacy of new therapies.
4. Anatomical models: These are physical representations of biological structures or systems, such as plastic models of organs or tissues, that can be used for educational purposes or to plan surgical procedures. They can also serve as a basis for developing more sophisticated models, such as computer simulations or 3D-printed replicas.

Overall, biological models play a crucial role in advancing our understanding of biology and medicine, helping to identify new targets for therapeutic intervention, develop novel drugs and treatments, and improve human health.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Cyclin B2 is a type of cyclin protein that regulates the cell cycle, particularly at the G2 phase and the beginning of mitosis. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 1 (CDK1), which plays a crucial role in the transition from G2 phase to mitosis. The expression and activity of Cyclin B2 are tightly regulated during the cell cycle, and its dysregulation can lead to abnormal cell division and contribute to the development of cancer.

Up-regulation is a term used in molecular biology and medicine to describe an increase in the expression or activity of a gene, protein, or receptor in response to a stimulus. This can occur through various mechanisms such as increased transcription, translation, or reduced degradation of the molecule. Up-regulation can have important functional consequences, for example, enhancing the sensitivity or response of a cell to a hormone, neurotransmitter, or drug. It is a normal physiological process that can also be induced by disease or pharmacological interventions.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Flavonoids are a type of plant compounds with antioxidant properties that are beneficial to health. They are found in various fruits, vegetables, grains, and wine. Flavonoids have been studied for their potential to prevent chronic diseases such as heart disease and cancer due to their ability to reduce inflammation and oxidative stress.

There are several subclasses of flavonoids, including:

1. Flavanols: Found in tea, chocolate, grapes, and berries. They have been shown to improve blood flow and lower blood pressure.
2. Flavones: Found in parsley, celery, and citrus fruits. They have anti-inflammatory and antioxidant properties.
3. Flavanonols: Found in citrus fruits, onions, and tea. They have been shown to improve blood flow and reduce inflammation.
4. Isoflavones: Found in soybeans and legumes. They have estrogen-like effects and may help prevent hormone-related cancers.
5. Anthocyanidins: Found in berries, grapes, and other fruits. They have antioxidant properties and may help improve vision and memory.

It is important to note that while flavonoids have potential health benefits, they should not be used as a substitute for medical treatment or a healthy lifestyle. It is always best to consult with a healthcare professional before starting any new supplement regimen.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

Chromones are a type of chemical compound that contain a benzopyran ring, which is a structural component made up of a benzene ring fused to a pyran ring. They can be found in various plants and have been used in medicine for their anti-inflammatory, antimicrobial, and antitussive (cough suppressant) properties. Some chromones are also known to have estrogenic activity and have been studied for their potential use in hormone replacement therapy. Additionally, some synthetic chromones have been developed as drugs for the treatment of asthma and other respiratory disorders.

Seven cyclin-dependent kinase inhibitor proteins have been identified. They are p15, p16, p18, p19, p21, p27, and p57. These ... In mammals, p27, a cyclin-dependent kinase inhibitor protein, helps control CDK activity in G1. Also, the INK4 proteins help ... Bayrak A, Oktay K (May 2003). "The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian ... A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin- ...
... may refer to: CDKN1B, cyclin-dependent kinase inhibitor 1B ÄŒZ vz. 27, a pistol IFI27, interferon alpha-inducible protein 27 ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... p27−/− knockout phenotype show an overproduction of cells because cyclin D is not inhibited anymore, while p27−/− and cyclin D ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ... Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The ...
"Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ... It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ... Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... Small molecule inhibitors of the binding site between Skp2 and its substrate p27 have been discovered, and these inhibitors ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... Specifically, TGF-β1 prevents the interleukin(IL)-1- & interleukin-2-dependent proliferation in activated T cells, as well as ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27". Nephrol. Dial. Transplant. 18 Suppl 3 (90003): iii9-12 ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Cyclins function as activating subunits of enzymatic complex together with cyclin-dependent kinases (CDKs). Different cyclins ... and the Kip/Cip family of CDK-inhibitor proteins. Cyclin-A1 interacts with: CDC20, Cyclin-dependent kinase 2, E2F1, GNB2L1, ... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-157. doi:10.1038/sj.onc.1201252. PMID 9244350. Suzuki Y, Yoshitomo ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... See also CDK inhibitor for inhibitors of various CDKs. Cyclin-dependent kinase 4 has been shown to interact with: CDC37, CDKN1B ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... Yang W, Zhang A, Han Y, Su X, Chen Y, Zhao W (2021). "Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional ...
2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, ... 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ...
... primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression. These regulation ... Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is ... RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then inhibits cofilin, which effectively reorganizes the ... Due to pathophysiological overlap of RhoA and Rho-kinase in asthma, both RhoA and Rho-kinase have become promising new target ...
... discovering that the cyclin-dependent kinase inhibitor p27 is critical to OPC development, such that differentiation in ... "Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1". Genes ... Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency (News and Views and ... exploring the role of p27 in oligodendrocyte differentiation, to understand how myelin development occurs. She found that p27 ...
... embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors ( ... CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A ...
... leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G1-phase arrest, as seen in ... Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the ... The first breakthrough in efforts to find a potent, specific, competitive inhibitor of HMG CoA reductase occurred in 1976, when ... Lovastatin was the first specific inhibitor of HMG CoA reductase to receive approval for the treatment of hypercholesterolemia ...
In addition to p53 and Rb, cyclin dependent kinase inhibitors (CKIs), such as p21, p27, and p57, are also important for ... Immunoprecipitation kinase assays revealed that cyclin C has Rb kinase activity. Furthermore, unlike cyclins D and E, cyclin ... co-immunoprecipitation assays revealed that cyclin-dependent kinase 3 (cdk3) promotes G0 exit by forming a complex with cyclin ... Under normal conditions, the yeast cyclin-dependent kinase complex, Pho80-Pho85, inactivates the Pho4 transcription factor ...
"Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas". ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... Chiarle, R; Pagano, M; Inghirami, G (2001). "The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes ...
"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... The p27kip1 protein is involved in cell cycle regulation and belongs to the Cip/Kip family of cyclin dependent kinase(CDK) ... inhibitors. These inhibitors possess an N-terminal CDK-inhibitory domain which binds to the ATP binding pocket of the kinase ... This p27 cis-regulatory element is 114 nucleotides in length and is located at the very 5' end of the 5'UTR of the p27 mRNA. It ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Hall M, Peters G (1996). Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Advances ... Cyclins function as regulators of CDKs (cyclin-dependent kinase). Different cyclins exhibit distinct expression and degradation ... cyclin box domain for cyclin-dependent kinase (CDK) binding and CDK inhibitor binding; LxxLL binding motif for co-activator ...
... a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation". Molecular ... p27 CDKN1B Schwob E, Böhm T, Mendenhall MD, Nasmyth K (October 1994). "The B-type cyclin kinase inhibitor p40SIC1 controls the ... "The yeast cyclin-dependent kinase inhibitor Sic1 and mammalian p27Kip1 are functional homologues with a structurally conserved ... "In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... CKIs or CIP/KIP family members like the protein p21 and p27 act blocking and inhibiting the assembled C-CDKs binding complex ... Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...
A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus ... CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ...
Cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27, binds to and prevents the activation of CyclinE:Cdk2 by ... The G1 phase cyclin-dependent kinase works together with S phase cyclin-dependent kinase targeting p27 for degradation. In turn ... Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein ... Morgan, David O. (November 1997). "CYCLIN-DEPENDENT KINASES: Engines, Clocks, and Microprocessors". Annual Review of Cell and ...
Like all cyclin family members, cyclin E forms complexes with cyclin-dependent kinases. In particular, Cyclin E binds with CDK2 ... The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting ... Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively. Smad3, a key mediator of TGF-β pathway ... Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S ...
"Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ... "Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27". The EMBO Journal. 18 (19 ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. doi: ...
"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... Rosner M, Hengstschläger M (November 2004). "Tuberin binds p27 and negatively regulates its interaction with the SCF component ... Cyclin A2 belongs to the cyclin family, whose members regulate cell cycle progression by interacting with CDK kinases. Cyclin ... Wang Y, Prives C (Jul 1995). "Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases ...
Singh R, Bhardwaj VK, Sharma J, Das P, Purohit R (March 2021). "Identification of selective cyclin-dependent kinase 2 inhibitor ... For example, the retinoblastoma (Rb) and p27 proteins are phosphorylated by Cdk2 - cyclin A/E complexes, fully deactivating ... Cyclin-dependent kinase 2 has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ...
September 2009). "Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases ... Nuclear PFKFB3 activates Cdk1 to phosphorylate the Thr-187 site of p27, causing decreased levels of p27. Reduced p27 causes ... April 2015). "Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3". Journal of Medicinal ... and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3's synthesis of F2,6BP in the nucleus was found ...
This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also ... May 2002). "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)". Oncogene. 21 (19): 3003-10. doi:10.1038/sj.onc. ... Tomoda K, Kubota Y, Kato J (March 1999). "Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1". ... May 2002). "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)". Oncogene. 21 (19): 3003-10. doi:10.1038/sj.onc. ...
"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ... September 1993). "Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in ... "Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1". Mammalian ...
CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). In this study we tested the expression of ... Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16). Expression of p15, p16, p21 and p27 did not vary in ... CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle ... Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). ...
Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. ... Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. Fred ... Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that ... our sequence analysis revealed that Cdi4 is a unique member of the p21/p27/p57 family of Cdk inhibitors. Our results ...
Seven cyclin-dependent kinase inhibitor proteins have been identified. They are p15, p16, p18, p19, p21, p27, and p57. These ... In mammals, p27, a cyclin-dependent kinase inhibitor protein, helps control CDK activity in G1. Also, the INK4 proteins help ... Bayrak A, Oktay K (May 2003). "The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian ... A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin- ...
3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces cell death in both striatum ... 3-NP reduced the level of cyclin-dependent kinase inhibitor p27 in striatum but not in cerebral cortex. 3-NP also induced ... Cyclin-Dependent Kinase Inhibitor p27 / antagonists & inhibitors * Cyclin-Dependent Kinase Inhibitor p27 / metabolism* ... Pharmacological experiments revealed that cyclin-dependent kinase activity and N-methyl-d-aspartate (NMDA) receptor were ...
Cyclin-Dependent Kinase Inhibitor p27 / genetics * Cyclin-Dependent Kinase Inhibitor p27 / metabolism ... Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), ... Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC. ... Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression ...
The CDKN1B gene provides instructions for making a protein called p27. Learn about this gene and related health conditions. ... cyclin-dependent kinase inhibitor 1B. *cyclin-dependent kinase inhibitor 1B (p27, Kip1) ... Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma ... Based on this function, p27 is described as a tumor suppressor protein. Studies suggest that p27 is also involved in ...
... modulating SASP and restoration of senescence inhibitors. In this review, we discuss current understanding of the role and ... modulating SASP and restoration of senescence inhibitors. In this review, we discuss current understanding of the role and ... 2003). Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and ... accumulation of tumor suppressor p53 and its downstream cyclin-dependent kinase (CDK) inhibitors (CKI) such as p21Cip1 (p21) ...
The Xenopus p27(Xic1) gene encodes a cyclin dependent kinase (CDK) inhibitor of the Cip/Kip family. We have previously shown ... Depletion of the cell-cycle inhibitor p27(Xic1) impairs neuronal differentiation and increases the number of ElrC(+) progenitor ... The X. tropicalis p27(Xic1) was expressed in a similar pattern to the X. laevis gene. Depletion of p27(Xic1) in X. tropicalis ... The expression of p27(Xic1) in the embryo is regionalised but the transcriptional regulation of p27(Xic1) is not well ...
Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p27, Estrogen Receptor alpha, Female, Gene Expression Regulation, ... targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. ... p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. p27 can undergo phosphorylation at serine 10 ... Adult, Age Factors, Aged, Aged, 80 and over, Cell Cycle, Cell Proliferation, Cyclin D1, ...
Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth. GP Ilyin, D ... The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis. L Erdtmann, N Franck, H Lerat, J Le Seyec, D ... ERK-dependent induction of TNFα expression by the environmental contaminant benzo (a) pyrene in primary human macrophages. V ... Overexpression of active Aurora-C kinase results in cell transformation and tumour formation. J Khan, F Ezan, JY Cr met, A ...
p21 and p27 are two important cyclin-dependent kinase (CDK) inhibitors and negative regulators of the G1-to-S phase transition ... HPK1 inhibits cell proliferation and increases the expression of cyclin-dependent kinase inhibitors p21 and p27. To investigate ... Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress ... Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by ...
... in ovarian cancer cells mediated through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1-Cullin-F-box protein/ ... inhibitors P21 and P27 [26,27]. 1,25(OH)2D can also induce cell cycle arrest at the G2/M checkpoint acting primarily on GADD45 ... Cyclin dependent kinase transcription is stimulated by the epidermal growth factor (EGF) which leads to the activation of E2F, ... Ovarian cancer cells can be arrested in the G1/S checkpoint by the action of calcitriol on cyclin-dependent kinase (CDK) ...
Using an adenoviral vector that encodes cyclin-dependent kinase inhibitor p27 with target sequences for EC-specific miR-126-3p ... PI3 is phosphoinositide 3-kinase; Akt is serine/threonine kinase; p53 is p53 protein. ... Moreover in this population the use of miravirsen has showed prolonged dose-dependent reductions in HCV RNA levels without ... In fact insulin-dependent T2DM patients have a worse functional recovery and a worse prognosis after CRT [18, 19, 21-24]. These ...
We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27Kip1 (p27) with target sequences for EC- ... Santulli and colleagues generated an adenovirus that expresses the cyclin-dependent kinase inhibitor p27Kip1 (p27) and bears ... As a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors, p27 binds and modulates cyclin D-, E- and A- ... Differential effects of the cyclin-dependent kinase inhibitors p27(Kip1), p21(Cip1), and p16(Ink4) on vascular smooth muscle ...
SGK1-sensitive regulation of cyclin-dependent kinase inhibitor 1B (p27) in cardiomyocyte hypertrophy. Cell Physiol Biochem 2015 ... Peng K, Tian X, Qian Y, Skibba M, Zou C, Liu Z, Wang J, Xu Z, Li X, Liang G: Novel EGFR inhibitors attenuate cardiac ... A recent study showed that Res may attenuate left ventricular hypertrophy via inhibiting NFAT-dependent transcription and ... of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. Cell ...
Expression of p27(Kip1), a Cyclin-Dependent Kinase Inhibitor, in Human Peripheral Blood Mononuclear Cells Is Inversely ...
The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) ... inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 ... the cyclin E protein and cyclin E-CDK complexes remained constant throughout the first 24 hr, implying that the cyclin E ... Cyclin E cDNA, cloned from a zebrafish embryonic cDNA library, was used for analysis of cyclin E regulation during early ...
... arrested cell cycle at G2/M phase with concomitant increase in the expression of cyclin-dependent kinase inhibitors p21 and p27 ... Moreover, this peptide decreases expression of cyclins and cyclin dependent kinases-4 and -6, implicated in cell cycle pathways ... The role of other soy protease inhibitors such as Kunitz Trypsin Inhibitor (KTI) cannot be excluded from these experiments. ... Inhibitors of these enzymes are becoming potential targets for new therapies.. METHODS AND RESULTS:. This study reports by ...
... which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. The protein is involved in ... Proton pump inhibitors for symptomatic control of symptomatic peptic ulcer disease due to hypergastrinemia ...
p27 is a member of the Kip family of cyclin-dependent kinase inhibitors and its overexpression results in cell cycle arrest at ... designed from human p27 cDNA resulted in efficient inhibition of p27 expression, while p27 shRNA designed from mouse p27 cDNA ... Immunostaining of p27 in MDA-MB-231 cells showed that p27 predominantly localized in the nuclei. These results suggest that ... To further elucidate the role of p27 in the motility of MDA-MB-231 breast cancer cells, we performed p27 knockdown in MDA-MB- ...
Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J. ... Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J. ... Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. Genes ... Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. Genes ...
... and by negatively regulating the cyclin-dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a ... LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis ... This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive ... Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) ...
The cyclin dependent kinase inhibitor p27 is one of the most frequently dysregulated tumour suppressor protein in human cancers ... A reduction in the level of cellular p27 is frequently due to increased proteasome-dependent degradation. Recently, studies ... show that the macrocyclic octapeptide argyrin A induced an increase in cellular p27 levels by preventing the turnover of the ...
... cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, ... cyclin-dependent kinase inhibitor MeSH Terms. Animals. Cell Cycle. Codon, Nonsense. Cyclin-Dependent Kinase Inhibitor p16. DNA ... Cyclin-Dependent Kinase Inhibitor p16. DNA. Phosphotransferases. Figure. *. Figure 1 TALEN-mediated generation of a p16Ink4a ... Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. ...
Expression of cyclin-dependent kinase inhibitor protein, p27(Kip1), precedes withdrawal of retinal cells from the cell cycle, ... Treatment is dependent upon the agent ingested and the presence or absence of esophageal damage. Seizure Brief partial seizure ...
... and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27(Kip1). ... a cyclin-dependent kinase inhibitor previously implicated as a direct target of miR-17 microRNAs. Knockdown of p21 in MLL- ... Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase that participates in numerous signalling ... Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy NATURE Wang, Z., Smith, K. S., Murphy, M., Piloto ...
... cyclin-dependent kinase (CDK) promotes cell cycle progression by forming complexes with cyclins, whereas the CDK inhibitors p21 ... Low levels of Hes1 promote cell proliferation by downregulating p21 and p27 (Murata et al.,2005). However, persistent and high ... Somite segmentation (Notch-dependent) (Pasini et al., 2004) her7 PSM (cyclic) Somite segmentation (Notch-dependent) (Oates and ... Somite segmentation (Notch-dependent) (Pasini et al., 2004) her7 PSM (cyclic) Somite segmentation (Notch-dependent) (Oates and ...
... and FoxO3-dependent G1 arrest and apoptosis in ECs via transcriptional activation of the cyclin-dependent kinase inhibitor p27 ... ribosyltransferase that directly inhibits Src kinase by simultaneous amidation and ADP ribosylation of the conserved kinase- ... Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at ... This leads to recruitment of the Nck-WIP-N-WASP complex that triggers Arp2/3-dependent actin polymerization in the host cell. ...
RAPA decreased the protein levels of cyclin dependent kinase 4 (CDK4) and increased the expression of the CDK inhibitor p27. In ... Syk Activation of Phosphatidylinositol 3-Kinase/Akt Prevents HtrA2-dependent Loss of X-linked Inhibitor of Apoptosis Protein ( ... phosphatidylinositol 3-kinase/Akt, and the mitogen-activated protein kinases (MAPK) p38, c-Jun N-terminal kinase (JNK), and ... An mTORC1/2 inhibitor and a PI3K/mTOR dual inhibitor suppressed Akt phosphorylation and showed a greater anti-proliferative ...
  • Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. (nih.gov)
  • Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. (nih.gov)
  • Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
  • The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). (koreamed.org)
  • Primary mouse embryo fibroblasts lacking Cip1 and Kip1 genes encoding inhibitors of cyclin-dependent kinase-2 were used to further explore the effects of oncogenic Ras on arrest of the cell division cycle. (ku.dk)
  • Although early passage primary fibroblast strains that lack both p21(Cip1) and p27(Kip1) fail to assemble cyclin D-dependent kinases, oncogenic Ras retained its ability to induce p19(ARF), but not p16(INK4a), protecting Cip/Kip-null cells from proliferating and undergoing transformation. (ku.dk)
  • Therefore, in the absence of p16(INK4a), p21(Cip1), and p27(Kip1), oncogenic Ras affects the functions of genes required for completion of the cell cycle. (ku.dk)
  • Background: The expression of the negative cell cycle regulator p27 Kip1 is frequently found to be deregulated in various human cancer types. (uni-luebeck.de)
  • Whether the expression of p27 Kip1 can be used as a prognostic marker for renal cell cancer patients still remains to be clarified. (uni-luebeck.de)
  • Patients and Methods: For analysis of p27 Kip1 expression in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising 1260 tissue samples each obtained from the tumor itself, the invasive front as well as the non-malignant surrounding parenchyma. (uni-luebeck.de)
  • Results: In univariate survival analysis, decreased expression of p27 Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p=0.02, log rank test). (uni-luebeck.de)
  • In contrast, expression of p27 Kip1 within the primary tumors was not identified to reveal any prognostically important information. (uni-luebeck.de)
  • 0.01) as well as decreased expression of p27 Kip1 (p=0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. (uni-luebeck.de)
  • Conclusion: Our analysis demonstrated that p27 Kip1 is heterogeneously expressed in renal cell carcinomas. (uni-luebeck.de)
  • Moreover, the results of the present study supports the prognostic value of p27 Kip1 protein expression for patients diagnosed with renal cell carcinoma. (uni-luebeck.de)
  • Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27 kip1 , but not p21 cip1 , causes faster turnover of invadopodia and increased ECM degradation. (biorxiv.org)
  • Furthermore, both endogenous and over-expressed p27 kip1 localizes to the sites of invadopodia assembly. (biorxiv.org)
  • In recent years, cell cycle regulators have been shown to exhibit roles in both tumor suppression and tumor promotion, particularly cyclin-dependent kinase inhibitors (CKI) p27 kip1 and p21 cip1 14 . (biorxiv.org)
  • Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)
  • In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). (duke.edu)
  • PD-1 suppressed the transcription of SKP2 , the substrate recognition component of the SCF Skp2 ubiquitin ligase that leads p27 kip1 to degradation and resulted in accumulation of p27 kip1 (Figure 2). (shu.edu)
  • What are the effects of p27 kip1 and p15 INK4 ? (shu.edu)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (merckmanuals.com)
  • C) Semi-quantitative PCR analysis for p27 transcript in the liver of WT and p27Kip1 KO mouse. (koreamed.org)
  • Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
  • We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. (fhcrc.org)
  • Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor proteins work by inactivating the CDKs by degradation. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor proteins use ATP as a phosphate contributor to phosphorylate serine and threonine residues. (wikipedia.org)
  • Seven cyclin-dependent kinase inhibitor proteins have been identified. (wikipedia.org)
  • The discovery of Cyclin-dependent kinase inhibitor proteins in 1990 opened the door in how we think about cell cycle control. (wikipedia.org)
  • The active cyclin/CDK complex then phosphorylates proteins, activates them, and sends the cell into the next phase of the cell cycle. (wikipedia.org)
  • Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (medlineplus.gov)
  • Some mutations impair the protein's ability to interact with regulatory proteins, while others lead to the production of an unstable version of p27 that is quickly broken down. (medlineplus.gov)
  • A key feature of prostate cancer progression is the induction and activation of survival proteins, including the Inhibitor of Apoptosis (IAP) family member survivin. (oncotarget.com)
  • The CDKN1B gene provides instructions for making a protein called p27. (medlineplus.gov)
  • Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. (medlineplus.gov)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. (wikipedia.org)
  • These results suggest that 3-NP induces aberrant cell cycle progression and neuronal cell death via p27 down-regulation by calpain in striatum but not in the cerebral cortex. (nih.gov)
  • By blocking cell cycle progression, p27 prevents cells from dividing too quickly or at the wrong time. (medlineplus.gov)
  • For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. (medlineplus.gov)
  • In addition to its role as a regulator of cell cycle progression, p27 can also participate in cell motility, especially when it is mislocalized in the cytosol. (spandidos-publications.com)
  • Cell cycle progression is governed by a complex network of cyclin-dependent kinases that define not only the phase of the cell cycle, but also the timing of transitions between phases 13 . (biorxiv.org)
  • The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (affbiotech.cn)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • Accumulation of p27 in the nucleus, therefore, blocks cell cycle progression of T-lymphocytes that are being induced to act against cancer antigens. (shu.edu)
  • S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. (umass.edu)
  • Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. (aacrjournals.org)
  • A reduction in the level of cellular p27 is frequently due to increased proteasome-dependent degradation. (nottingham.ac.uk)
  • Moreover, transfection of p27 small interfering RNA reduced striatal cell viability. (nih.gov)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.org)
  • p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
  • We have determined crystal structures of the Cdk2-Spy1 and p27-Cdk2-Spy1 complexes that reveal how Spy1 activates Cdk. (escholarship.org)
  • Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (affbiotech.cn)
  • Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. (affbiotech.cn)
  • The structure of CDK2-CyclinA and p27 is determined by crystallography, demonstrating that the inhibitor of p27 stretches at the top of the Cyclin-CDK complex. (wikipedia.org)
  • p27 slides into the ATP- binding site of CDK2 and inhibits ATP binding. (wikipedia.org)
  • Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. (affbiotech.cn)
  • It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. (duke.edu)
  • To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4(D158N) mice. (duke.edu)
  • p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
  • It also blocks Cyclin A-CDK2 from further phosphorylating pRb to maintain S phase. (shu.edu)
  • The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
  • Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
  • Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)
  • SKP2 overexpression is associated with increased serine 10 phosphorylation of p27 (pSer10p27) in triple-negative breast cancer. (umass.edu)
  • p27 can undergo phosphorylation at serine 10 (pSer10p27). (umass.edu)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
  • Human cells contain many different cyclins binding to different CDKs. (wikipedia.org)
  • CDKs and cyclins appear and activate at specific cell cycle phases. (wikipedia.org)
  • Further research has demonstrates that Cdks, cyclins and CKIs play essential roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. (wikipedia.org)
  • Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
  • All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. (medlineplus.gov)
  • Indeed, while X. laevis has two p27(Xic1) paralogs, p27(Xic1) and p28(Kix1), we have found only one ortholog in X. tropicalis, equidistant from the X. laevis genes. (xenbase.org)
  • Immunohistochemistry (IHC) of SKP2, p27, pSer10p27, and other genes involved in this pathway, was analyzed in 188 breast tumors and 50 benign reduction mammoplasty samples. (umass.edu)
  • Results: Data addressing the function of vectors harbouring genes specifically encoding ricin, saporin, lunasin , linamarase, and tomato thymidine kinase 1 under the control of different promoters are summarised here. (weeksmd.com)
  • During the first 10 postnatal days, administration of valproic acid (VPA), the specific inhibitor for histone deacetylase activity, resulted in significant hypomyelination with delayed expression of late differentiation markers and retained expression of progenitor markers. (rupress.org)
  • However, if CKI's mutations don't stop the cell, the Cyclin D is transcribed. (wikipedia.org)
  • Still other mutations prevent p27 from moving from the cytoplasm into the nucleus. (medlineplus.gov)
  • Like the mutations that cause multiple endocrine neoplasia type 4, these genetic changes reduce the amount of functional p27 available to control cell division. (medlineplus.gov)
  • Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. (koreamed.org)
  • A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. (wikipedia.org)
  • The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. (duke.edu)
  • These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)
  • P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
  • Full holoenzyme activity of the cyclin D1-Cdk4 complex is induced by mitogen recruitment of CAK. (shu.edu)
  • In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. (biomedcentral.com)
  • Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
  • p15, p16, p21 and p27 in mouse ovaries by immunohistochemistry to assess whether the initiation of primordial follicle growth was associated with the expression of CDKIs. (biomedcentral.com)
  • The expression of p27(Xic1) in the embryo is regionalised but the transcriptional regulation of p27(Xic1) is not well understood. (xenbase.org)
  • We report the isolation of a p27(Xic1) genomic clone and we identify a 5' region capable of driving reporter gene expression specifically in the neural tube and the eye. (xenbase.org)
  • Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. (aacrjournals.org)
  • After MG132 withdrawal, wild-type HPK1 protein expression was markedly decreased within 24 hours, but kinase-dead HPK1 mutant protein expression was sustained for up to 96 hours. (aacrjournals.org)
  • Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. (aacrjournals.org)
  • Histone deacetylation was essential during a specific temporal window of development and was dependent on the enzymatic activity of histone deacetylases, whose expression was detected in the developing corpus callosum. (rupress.org)
  • Infection of MDA-MB-231 cells with retroviruses harboring p27 short hairpin RNA (shRNA) designed from human p27 cDNA resulted in efficient inhibition of p27 expression, while p27 shRNA designed from mouse p27 cDNA did not affect p27 expression in MDA-MB-231 cells. (spandidos-publications.com)
  • Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)
  • In the cyclin-dependent kinase (CDK) family or CDK, Cyclin, and CKIs, serine/threonine kinases play an integral role in regulating the eukaryotic cell cycle. (wikipedia.org)
  • Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
  • In animals, CDK inhibitors are tightly regulated, especially by posttranslational mechanisms of which control of nuclear access and regulation of protein turnover are particularly important. (uni-bielefeld.de)
  • Here we address the posttranslational regulation of INHIBITOR/INTERACTOR OF CDK 1 (ICK1)/KIP RELATED PROTEIN 1 ( KRP1), an Arabidopsis ( Arabidopsis thaliana) CDK inhibitor. (uni-bielefeld.de)
  • Herpes virus thymidine kinase (HSV-tk) is used in suicide gene therapy. (umich.edu)
  • Lyoma virus enhancer, HSV-tk enhancer and promoter, HSV thymidine kinase. (umich.edu)
  • Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. (aacrjournals.org)
  • p27 is a member of the Kip family of cyclin-dependent kinase inhibitors and its overexpression results in cell cycle arrest at G1 and/or apoptosis. (spandidos-publications.com)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.com)
  • These cyclin-dependent kinase inhibitor protein emerges only in their specific cell cycle phase. (wikipedia.org)
  • Each Cyclin/CDK complex are specific to the part of the cell cycle phase. (wikipedia.org)
  • Specifically, p27 normally blocks cells from entering the phase of the cell cycle when DNA is copied (replicated) in preparation for cell division. (medlineplus.gov)
  • It moves into the cytoplasm and eventually activates a specific cyclin-dependent kinase (CDK). (wikipedia.org)
  • Whereas p16(INK4a) antagonizes the activities of cyclin D-dependent kinases, p19(ARF) activates the p53 transcription factor. (ku.dk)
  • Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that it interacts with cyclin E strengthened the notion that it functions in cell cycle regulation. (fhcrc.org)
  • Both striatal p27 down-regulation and cell death provoked by 3-NP were dependent on calpain activity. (nih.gov)
  • However, changes in regulation that reduce the amount or function of the p27 protein in the nucleus are found in many types of cancer. (medlineplus.gov)
  • Depletion of p27(Xic1) in X. tropicalis caused an increase in proliferation and a suppression of the neuronal differentiation marker, N-tubulin. (xenbase.org)
  • MDA-MB-231 cells infected with human p27 shRNA (MDA-MB-231 hp27shRNA) showed increased proliferation compared to control MDA-MB-231 cells and MDA-MB-231 cells infected with mouse p27shRNA (MDA-MB-231 mp27shRNA). (spandidos-publications.com)
  • Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. (stanford.edu)
  • Our study demonstrates that survivin and APE1/Ref-1 are significantly higher in human prostate cancer specimens compared to noncancerous controls and that APE1/Ref-1 redox-specific inhibition with small molecule inhibitor, APX3330 and a second-generation inhibitor, APX2009, decreases prostate cancer cell proliferation and induces cell cycle arrest. (oncotarget.com)
  • Recently, studies show that the macrocyclic octapeptide argyrin A induced an increase in cellular p27 levels by preventing the turnover of the protein via inhibition of proteasome function. (nottingham.ac.uk)
  • Studies suggest that p27 is also involved in controlling cell differentiation, which is the process by which cells mature to carry out specific functions. (medlineplus.gov)
  • Depletion of the cell-cycle inhibitor p27 ( Xic1 ) impairs neuronal differentiation and increases the number of ElrC (+) progenitor cells in Xenopus tropicalis. (xenbase.org)
  • To investigate whether p27(Xic1) is necessary for cell cycle exit and/or neuronal differentiation, we used antisense morpholino oligos (MO) to knockdown the protein levels in vivo. (xenbase.org)
  • In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. (uni-wuerzburg.de)
  • Together, the results indicate that presence of high SKP2 plus high pSer10p27 levels in triple-negative breast cancers is associated with aggressive growth, and highlight the validity of using SKP2 inhibitors as a therapeutic approach for treating this subset of breast cancers. (umass.edu)
  • To further elucidate the role of p27 in the motility of MDA-MB-231 breast cancer cells, we performed p27 knockdown in MDA-MB-231 cells by RNA interference. (spandidos-publications.com)
  • Role in cancer: Cyclin-dependent kinase inhibitors (CKIs) mutants are frequent in human cancers. (wikipedia.org)
  • The cyclin dependent kinase inhibitor p27 is one of the most frequently dysregulated tumour suppressor protein in human cancers. (nottingham.ac.uk)
  • p16 is a cyclin-dependent kinase inhibitor that has shown prognostic utility in some human cancers. (umich.edu)
  • 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces cell death in both striatum and cerebral cortex. (nih.gov)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)
  • We have previously shown that p27(Xic1) is expressed in the cells of the neural plate as they become post-mitotic (Development 127 (2000) 1303). (xenbase.org)
  • Researchers believe that p27 may have other functions in the cytoplasm, but these functions have not been well described. (medlineplus.gov)
  • The Xenopus p27(Xic1) gene encodes a cyclin dependent kinase (CDK) inhibitor of the Cip/Kip family. (xenbase.org)
  • The X. tropicalis p27(Xic1) was expressed in a similar pattern to the X. laevis gene. (xenbase.org)
  • This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (affbiotech.cn)
  • Because p27 plays such a key role in controlling cell division, its activity is tightly regulated. (medlineplus.gov)
  • In mammals, p27, a cyclin-dependent kinase inhibitor protein, helps control CDK activity in G1. (wikipedia.org)
  • Pharmacological experiments revealed that cyclin-dependent kinase activity and N-methyl-d-aspartate (NMDA) receptor were cooperatively involved in cell death by 3-NP in striatal neurons, whereas only NMDA receptor was involved in 3-NP-induced neurotoxicity in cortical neurons. (nih.gov)
  • In cortical neurons, however, there was no change in somatic Ca(2+) and calpain activity by 3-NP, and calpain inhibitors were not protective. (nih.gov)
  • A shortage of p27 has been associated with more aggressive tumors and a poorer prognosis. (medlineplus.gov)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in samples from tissue homogenates or other biological fluids. (jemsec.com)
  • Description: A sandwich ELISA for quantitative measurement of Human Cyclin dependent kinase inhibitor 3(CDKN3) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. (jemsec.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in Tissue homogenates and other biological fluids. (jemsec.com)
  • Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. (medlineplus.gov)
  • In light of these results, our sequence analysis revealed that Cdi4 is a unique member of the p21/p27/p57 family of Cdk inhibitors. (fhcrc.org)