Cyclin dependent kinase 6. Medical search

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 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.

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.

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 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 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.

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.

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.

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.

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 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 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.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

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 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.

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 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.

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 broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.

A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

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.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

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.

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.

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.

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.

Agents that inhibit PROTEIN KINASES.

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.

A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.

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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

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 fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

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.

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.

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 widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.

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.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.

A cell line derived from cultured tumor cells.

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.

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.

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 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 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.

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.

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.

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.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

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 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.

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.

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)

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.

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.

Established cell cultures that have the potential to propagate indefinitely.

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.

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.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

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.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

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.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

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.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

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.

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.

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 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.

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.

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.

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 biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.

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.

A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.

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 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.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.

An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.

The rate dynamics in chemical or physical systems.

A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).

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.

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 transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.

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.

A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.

A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.

A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.

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 parts of a macromolecule that directly participate in its specific combination with another molecule.

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 family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.

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).

An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Elements of limited time intervals, contributing to particular results or situations.

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.

A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.

A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.

A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.

ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.

A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

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.

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.

A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.

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.

An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.

A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.

A group of phenyl benzopyrans named for having structures like FLAVONES.

Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.

A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.

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.

An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.

Proteins prepared by recombinant DNA technology.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.

A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.

A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.

The process by which a DNA molecule is duplicated.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.

A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.

A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.

A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.

Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.

A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

The relationship between the dose of an administered drug and the response of the organism to the drug.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.

Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.

A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.

A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.

A family of non-receptor, PROLINE-rich protein-tyrosine kinases.

A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.

A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Derivatives of the steroid androstane having two double bonds at any site in any of the rings.

A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.

The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

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 B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.

Tumors or cancer of the human BREAST.

PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes

A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.

A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.

A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/363)

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)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/363)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +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. (3/363)

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)

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (4/363)

We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent. (+info)

NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. (5/363)

Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1. (+info)

Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8. (6/363)

Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, encodes a protein, referred to as HHV8-Vcyc, with sequence similarity to human G1 cyclins, in particular of the D type. HHV8-Vcyc is expressed in Kaposi's sarcoma and functional analysis suggests that it can activate cyclin-dependent kinases (cdk) and thereby trigger inactivation of the retinoblastoma protein (pRb), indicating that HHV8-Vcyc may contribute to the oncogenic potential of HHV-8. We show here that HHV8-Vcyc can activate transcription of the human cyclin A gene in quiescent cells, a property shared with known transforming oncogenes. Transcriptional activation by HHV8-Vcyc depends on an E2F-binding site in the cyclin A promoter, and cdk6 kinase activity is required. The ability of HHV8-Vcyc to activate cyclin A gene expression is shared by D-type cyclins and cyclin E. Unlike D-type cyclins, HHV8-Vcyc is unable to trigger phosphorylation of the pRb-related protein p107 and fails to induce dissociation of p107 from E2F. Unlike cyclin E, HHV8-Vcyc fails to interact physically with E2F complexes on the cyclin A promoter. These results provide additional evidence for the notion that the HHV-8-encoded cyclin differs in several properties from cellular G1 cyclins. (+info)

Anchorage dependence of mitogen-induced G1 to S transition in primary T lymphocytes. (7/363)

Anchorage dependence defines the cellular requirement for integrin-mediated adhesion to substrate to initiate DNA replication in response to growth factors. In this study we investigated whether normal T cells, which spend extended periods in a nonadherent state, show similar requirements for cell cycle progression in response to TCR stimulation. Resting primary T lymphocytes were induced to enter the cell cycle by TCR triggering, and leukocyte integrins were either engaged using purified ICAM-1 or inhibited with function-blocking mAbs. Our data indicate that leukocyte integrins complement TCR-driven mitogenic signals not as a result of their direct clustering but, rather, via integrin-dependent organization of the actin cytoskeleton. Leukocyte integrin-dependent reorganization of the actin cytoskeleton cooperates with the TCR to effect mitogen-activated protein kinase activation, but also represents a required late (4-8 h poststimulation) component in the mitogenic response of normal T cells. Prolonged leukocyte integrin-dependent spreading, in the context of intercellular contact, is a requisite for the production of the mitogenic cytokine IL-2, which, in turn, is involved in the induction of D3 cyclin and is primarily responsible for the decrease in the cyclin-dependent kinase inhibitor p27kip, resulting in retinoblastoma protein inactivation and S phase entry. Thus, T lymphocytes represent a peculiar case of anchorage dependence, in which signals conveyed by integrins act sequentially with the activating stimulus to effect a sustained production of the essential mitogenic cytokine. (+info)

CTLA-4-Mediated inhibition of early events of T cell proliferation. (8/363)

CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation. (+info)

There are different types of Breast Neoplasms such as:

1. Fibroadenomas: These are benign tumors that are made up of glandular and fibrous tissues. They are usually small and round, with a smooth surface, and can be moved easily under the skin.

2. Cysts: These are fluid-filled sacs that can develop in both breast tissue and milk ducts. They are usually benign and can disappear on their own or be drained surgically.

3. Ductal Carcinoma In Situ (DCIS): This is a precancerous condition where abnormal cells grow inside the milk ducts. If left untreated, it can progress to invasive breast cancer.

4. Invasive Ductal Carcinoma (IDC): This is the most common type of breast cancer and starts in the milk ducts but grows out of them and invades surrounding tissue.

5. Invasive Lobular Carcinoma (ILC): It originates in the milk-producing glands (lobules) and grows out of them, invading nearby tissue.

Breast Neoplasms can cause various symptoms such as a lump or thickening in the breast or underarm area, skin changes like redness or dimpling, change in size or shape of one or both breasts, discharge from the nipple, and changes in the texture or color of the skin.

Treatment options for Breast Neoplasms may include surgery such as lumpectomy, mastectomy, or breast-conserving surgery, radiation therapy which uses high-energy beams to kill cancer cells, chemotherapy using drugs to kill cancer cells, targeted therapy which uses drugs or other substances to identify and attack cancer cells while minimizing harm to normal cells, hormone therapy, immunotherapy, and clinical trials.

It is important to note that not all Breast Neoplasms are cancerous; some are benign (non-cancerous) tumors that do not spread or grow.

Explanation: Neoplastic cell transformation is a complex process that involves multiple steps and can occur as a result of genetic mutations, environmental factors, or a combination of both. The process typically begins with a series of subtle changes in the DNA of individual cells, which can lead to the loss of normal cellular functions and the acquisition of abnormal growth and reproduction patterns.

Over time, these transformed cells can accumulate further mutations that allow them to survive and proliferate despite adverse conditions. As the transformed cells continue to divide and grow, they can eventually form a tumor, which is a mass of abnormal cells that can invade and damage surrounding tissues.

In some cases, cancer cells can also break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body, where they can establish new tumors. This process, known as metastasis, is a major cause of death in many types of cancer.

It's worth noting that not all transformed cells will become cancerous. Some forms of cellular transformation, such as those that occur during embryonic development or tissue regeneration, are normal and necessary for the proper functioning of the body. However, when these transformations occur in adult tissues, they can be a sign of cancer.

See also: Cancer, Tumor

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1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Neoplasm refers to an abnormal growth of cells that can be benign (non-cancerous) or malignant (cancerous). Neoplasms can occur in any part of the body and can affect various organs and tissues. The term "neoplasm" is often used interchangeably with "tumor," but while all tumors are neoplasms, not all neoplasms are tumors.

Types of Neoplasms

There are many different types of neoplasms, including:

1. Carcinomas: These are malignant tumors that arise in the epithelial cells lining organs and glands. Examples include breast cancer, lung cancer, and colon cancer.
2. Sarcomas: These are malignant tumors that arise in connective tissue, such as bone, cartilage, and fat. Examples include osteosarcoma (bone cancer) and soft tissue sarcoma.
3. Lymphomas: These are cancers of the immune system, specifically affecting the lymph nodes and other lymphoid tissues. Examples include Hodgkin lymphoma and non-Hodgkin lymphoma.
4. Leukemias: These are cancers of the blood and bone marrow that affect the white blood cells. Examples include acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).
5. Melanomas: These are malignant tumors that arise in the pigment-producing cells called melanocytes. Examples include skin melanoma and eye melanoma.

Causes and Risk Factors of Neoplasms

The exact causes of neoplasms are not fully understood, but there are several known risk factors that can increase the likelihood of developing a neoplasm. These include:

1. Genetic predisposition: Some people may be born with genetic mutations that increase their risk of developing certain types of neoplasms.
2. Environmental factors: Exposure to certain environmental toxins, such as radiation and certain chemicals, can increase the risk of developing a neoplasm.
3. Infection: Some neoplasms are caused by viruses or bacteria. For example, human papillomavirus (HPV) is a common cause of cervical cancer.
4. Lifestyle factors: Factors such as smoking, excessive alcohol consumption, and a poor diet can increase the risk of developing certain types of neoplasms.
5. Family history: A person's risk of developing a neoplasm may be higher if they have a family history of the condition.

Signs and Symptoms of Neoplasms

The signs and symptoms of neoplasms can vary depending on the type of cancer and where it is located in the body. Some common signs and symptoms include:

1. Unusual lumps or swelling
2. Pain
3. Fatigue
4. Weight loss
5. Change in bowel or bladder habits
6. Unexplained bleeding
7. Coughing up blood
8. Hoarseness or a persistent cough
9. Changes in appetite or digestion
10. Skin changes, such as a new mole or a change in the size or color of an existing mole.

Diagnosis and Treatment of Neoplasms

The diagnosis of a neoplasm usually involves a combination of physical examination, imaging tests (such as X-rays, CT scans, or MRI scans), and biopsy. A biopsy involves removing a small sample of tissue from the suspected tumor and examining it under a microscope for cancer cells.

The treatment of neoplasms depends on the type, size, location, and stage of the cancer, as well as the patient's overall health. Some common treatments include:

1. Surgery: Removing the tumor and surrounding tissue can be an effective way to treat many types of cancer.
2. Chemotherapy: Using drugs to kill cancer cells can be effective for some types of cancer, especially if the cancer has spread to other parts of the body.
3. Radiation therapy: Using high-energy radiation to kill cancer cells can be effective for some types of cancer, especially if the cancer is located in a specific area of the body.
4. Immunotherapy: Boosting the body's immune system to fight cancer can be an effective treatment for some types of cancer.
5. Targeted therapy: Using drugs or other substances to target specific molecules on cancer cells can be an effective treatment for some types of cancer.

Prevention of Neoplasms

While it is not always possible to prevent neoplasms, there are several steps that can reduce the risk of developing cancer. These include:

1. Avoiding exposure to known carcinogens (such as tobacco smoke and radiation)
2. Maintaining a healthy diet and lifestyle
3. Getting regular exercise
4. Not smoking or using tobacco products
5. Limiting alcohol consumption
6. Getting vaccinated against certain viruses that are associated with cancer (such as human papillomavirus, or HPV)
7. Participating in screening programs for early detection of cancer (such as mammograms for breast cancer and colonoscopies for colon cancer)
8. Avoiding excessive exposure to sunlight and using protective measures such as sunscreen and hats to prevent skin cancer.

It's important to note that not all cancers can be prevented, and some may be caused by factors that are not yet understood or cannot be controlled. However, by taking these steps, individuals can reduce their risk of developing cancer and improve their overall health and well-being.

There are several types of lung neoplasms, including:

1. Adenocarcinoma: This is the most common type of lung cancer, accounting for approximately 40% of all lung cancers. It is a malignant tumor that originates in the glands of the respiratory tract and can be found in any part of the lung.
2. Squamous cell carcinoma: This type of lung cancer accounts for approximately 25% of all lung cancers and is more common in men than women. It is a malignant tumor that originates in the squamous cells lining the airways of the lungs.
3. Small cell lung cancer (SCLC): This is a highly aggressive form of lung cancer that accounts for approximately 15% of all lung cancers. It is often found in the central parts of the lungs and can spread quickly to other parts of the body.
4. Large cell carcinoma: This is a rare type of lung cancer that accounts for only about 5% of all lung cancers. It is a malignant tumor that originates in the large cells of the respiratory tract and can be found in any part of the lung.
5. Bronchioalveolar carcinoma (BAC): This is a rare type of lung cancer that originates in the cells lining the airways and alveoli of the lungs. It is more common in women than men and tends to affect older individuals.
6. Lymphangioleiomyomatosis (LAM): This is a rare, progressive, and often fatal lung disease that primarily affects women of childbearing age. It is characterized by the growth of smooth muscle-like cells in the lungs and can lead to cysts, lung collapse, and respiratory failure.
7. Hamartoma: This is a benign tumor that originates in the tissue of the lungs and is usually found in children. It is characterized by an overgrowth of normal lung tissue and can be treated with surgery.
8. Secondary lung cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
9. Metastatic cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
10. Mesothelioma: This is a rare and aggressive form of cancer that originates in the lining of the lungs or abdomen. It is caused by asbestos exposure and can be treated with surgery, chemotherapy, and radiation therapy.

Lung diseases can also be classified based on their cause, such as:

1. Infectious diseases: These are caused by bacteria, viruses, or other microorganisms and can include pneumonia, tuberculosis, and bronchitis.
2. Autoimmune diseases: These are caused by an overactive immune system and can include conditions such as sarcoidosis and idiopathic pulmonary fibrosis.
3. Genetic diseases: These are caused by inherited mutations in genes that affect the lungs and can include cystic fibrosis and primary ciliary dyskinesia.
4. Environmental diseases: These are caused by exposure to harmful substances such as tobacco smoke, air pollution, and asbestos.
5. Radiological diseases: These are caused by exposure to ionizing radiation and can include conditions such as radiographic breast cancer and lung cancer.
6. Vascular diseases: These are caused by problems with the blood vessels in the lungs and can include conditions such as pulmonary embolism and pulmonary hypertension.
7. Tumors: These can be benign or malignant and can include conditions such as lung metastases and lung cancer.
8. Trauma: This can include injuries to the chest or lungs caused by accidents or other forms of trauma.
9. Congenital diseases: These are present at birth and can include conditions such as bronchopulmonary foregut malformations and congenital cystic adenomatoid malformation.

Each type of lung disease has its own set of symptoms, diagnosis, and treatment options. It is important to seek medical attention if you experience any persistent or severe respiratory symptoms, as early diagnosis and treatment can improve outcomes and quality of life.

The prognosis for mantle-cell lymphoma is generally poor, with a five-year survival rate of approximately 40%. Treatment options include chemotherapy, immunotherapy, and autologous stem-cell transplantation. The disease often recurs after initial therapy, and subsequent treatments may be less effective.

Mantle-cell lymphoma can be difficult to distinguish from other types of non-Hodgkin lymphoma, such as follicular lymphoma or diffuse large B-cell lymphoma, and a correct diagnosis is important for determining appropriate treatment.

Slide: Mantle Cell Lymphoma (Image courtesy of Nephron/Wikimedia Commons)

1. Tumor size and location: Larger tumors that have spread to nearby tissues or organs are generally considered more invasive than smaller tumors that are confined to the original site.
2. Cellular growth patterns: The way in which cancer cells grow and divide can also contribute to the overall invasiveness of a neoplasm. For example, cells that grow in a disorganized or chaotic manner may be more likely to invade surrounding tissues.
3. Mitotic index: The mitotic index is a measure of how quickly the cancer cells are dividing. A higher mitotic index is generally associated with more aggressive and invasive cancers.
4. Necrosis: Necrosis, or the death of cells, can be an indication of the level of invasiveness of a neoplasm. The presence of significant necrosis in a tumor is often a sign that the cancer has invaded surrounding tissues and organs.
5. Lymphovascular invasion: Cancer cells that have invaded lymphatic vessels or blood vessels are considered more invasive than those that have not.
6. Perineural invasion: Cancer cells that have invaded nerve fibers are also considered more invasive.
7. Histological grade: The histological grade of a neoplasm is a measure of how abnormal the cancer cells look under a microscope. Higher-grade cancers are generally considered more aggressive and invasive than lower-grade cancers.
8. Immunohistochemical markers: Certain immunohistochemical markers, such as Ki-67, can be used to evaluate the proliferative activity of cancer cells. Higher levels of these markers are generally associated with more aggressive and invasive cancers.

Overall, the degree of neoplasm invasiveness is an important factor in determining the likelihood of the cancer spreading to other parts of the body (metastasizing) and in determining the appropriate treatment strategy for the patient.

There are several types of colonic neoplasms, including:

1. Adenomas: These are benign growths that are usually precursors to colorectal cancer.
2. Carcinomas: These are malignant tumors that arise from the epithelial lining of the colon.
3. Sarcomas: These are rare malignant tumors that arise from the connective tissue of the colon.
4. Lymphomas: These are cancers of the immune system that can affect the colon.

Colonic neoplasms can cause a variety of symptoms, including bleeding, abdominal pain, and changes in bowel habits. They are often diagnosed through a combination of medical imaging tests (such as colonoscopy or CT scan) and biopsy. Treatment for colonic neoplasms depends on the type and stage of the tumor, and may include surgery, chemotherapy, and/or radiation therapy.

Overall, colonic neoplasms are a common condition that can have serious consequences if left untreated. It is important for individuals to be aware of their risk factors and to undergo regular screening for colon cancer to help detect and treat any abnormal growths or tumors in the colon.

Malignant prostatic neoplasms are cancerous tumors that can be aggressive and spread to other parts of the body (metastasize). The most common type of malignant prostatic neoplasm is adenocarcinoma of the prostate, which accounts for approximately 95% of all prostate cancers. Other types of malignant prostatic neoplasms include sarcomas and small cell carcinomas.

Prostatic neoplasms can be diagnosed through a variety of tests such as digital rectal examination (DRE), prostate-specific antigen (PSA) test, imaging studies (ultrasound, CT scan or MRI), and biopsy. Treatment options for prostatic neoplasms depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health. Treatment options can include active surveillance, surgery (robotic-assisted laparoscopic prostatectomy or open prostatectomy), radiation therapy (external beam radiation therapy or brachytherapy), and hormone therapy.

In summary, Prostatic Neoplasms are tumors that occur in the prostate gland, which can be benign or malignant. The most common types of malignant prostatic neoplasms are adenocarcinoma of the prostate, and other types include sarcomas and small cell carcinomas. Diagnosis is done through a variety of tests, and treatment options depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health.

SCC typically appears as a firm, flat, or raised bump on the skin, and may be pink, red, or scaly. The cancer cells are usually well-differentiated, meaning they resemble normal squamous cells, but they can grow rapidly and invade surrounding tissues if left untreated.

SCC is more common in fair-skinned individuals and those who spend a lot of time in the sun, as UV radiation can damage the skin cells and increase the risk of cancer. The cancer can also spread to other parts of the body, such as lymph nodes or organs, and can be life-threatening if not treated promptly and effectively.

Treatment for SCC usually involves surgery to remove the cancerous tissue, and may also include radiation therapy or chemotherapy to kill any remaining cancer cells. Early detection and treatment are important to improve outcomes for patients with SCC.

Adenocarcinoma is a term used to describe a variety of different types of cancer that arise in glandular tissue, including:

1. Colorectal adenocarcinoma (cancer of the colon or rectum)
2. Breast adenocarcinoma (cancer of the breast)
3. Prostate adenocarcinoma (cancer of the prostate gland)
4. Pancreatic adenocarcinoma (cancer of the pancreas)
5. Lung adenocarcinoma (cancer of the lung)
6. Thyroid adenocarcinoma (cancer of the thyroid gland)
7. Skin adenocarcinoma (cancer of the skin)

The symptoms of adenocarcinoma depend on the location of the cancer and can include:

1. Blood in the stool or urine
2. Abdominal pain or discomfort
3. Changes in bowel habits
4. Unusual vaginal bleeding (in the case of endometrial adenocarcinoma)
5. A lump or thickening in the breast or elsewhere
6. Weight loss
7. Fatigue
8. Coughing up blood (in the case of lung adenocarcinoma)

The diagnosis of adenocarcinoma is typically made through a combination of imaging tests, such as CT scans, MRI scans, and PET scans, and a biopsy, which involves removing a sample of tissue from the affected area and examining it under a microscope for cancer cells.

Treatment options for adenocarcinoma depend on the location of the cancer and can include:

1. Surgery to remove the tumor
2. Chemotherapy, which involves using drugs to kill cancer cells
3. Radiation therapy, which involves using high-energy X-rays or other particles to kill cancer cells
4. Targeted therapy, which involves using drugs that target specific molecules on cancer cells to kill them
5. Immunotherapy, which involves using drugs that stimulate the immune system to fight cancer cells.

The prognosis for adenocarcinoma is generally good if the cancer is detected and treated early, but it can be more challenging to treat if the cancer has spread to other parts of the body.

Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ... Liu, Ji; Kipreos, Edward T. (2000). "Evolution of Cyclin-Dependent Kinases (CDKs) and CDK-Activating Kinases (CAKs): ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_6

... 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 ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_2

Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase. S-phase cyclin ... G1/S cyclin-Cdk complexes promote the destruction of Sic1 and allow activation of Clb5- and Clb6-Cdk1 complexes. As the yeast ... In this hypothesis, cyclin concentrations must rise and accumulate to proceed to the next stage of the cell cycle. In mitotic ... Clb5 and Clb6 levels rise during G1 (earlier than other B-type cyclins) and stay high throughout S and M phases. During S-phase ...

https://en.wikipedia.org/wiki/Clb_5,6_(Cdk1)

"MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6". World J Surg ...

https://en.wikipedia.org/wiki/MicroRNA_495

... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ... Overview of all the structural information available in the PDB for UniProt: P06493 (Cyclin-dependent kinase 1) at the PDBe-KB ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_1

"Entrez Gene: CDK10 cyclin-dependent kinase (CDC2-like) 10". Kasten M, Giordano A (Apr 2001). "Cdk10, a Cdc2-related kinase, ... Cyclin-dependent kinase 10 has been shown to interact with ETS2. GRCh38: Ensembl release 89: ENSG00000185324 - Ensembl, May ... This kinase has been shown to play a role in cellular proliferation. Its function is limited to cell cycle G2-M phase. At least ... Cell division protein kinase 10 is an enzyme that in humans is encoded by the CDK10 gene. The protein encoded by this gene ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_10

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_7

... ; CDK5". omim.org. Retrieved 2020-11-02. Tsai, Li-Huei. Cyclin Dependent Kinase 5 (Cdk5). Bibb JA ( ... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... The molecule belongs to the cyclin-dependent kinase family. Kinases are enzymes that catalyze reactions of phosphorylation. ... Cyclin-dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. It was discovered 15 ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_5

"Entrez Gene: CDK3 cyclin-dependent kinase 3". Bullrich F, MacLachlan TK, Sang N, et al. (1995). "Chromosomal mapping of members ... 2002). "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". Eur. J. Biochem. 268 (23): 6076-82. doi:10.1046/j. ... Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J ... Ren S, Rollins BJ (2004). "Cyclin C/cdk3 promotes Rb-dependent G0 exit". Cell. 117 (2): 239-51. doi:10.1016/S0092-8674(04)00300 ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_3

"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8". Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Cyclin-dependent kinase 8 has been shown to interact with: CCNC CREB binding protein CRSP3 MED1 MED12 MED14 MED16 MED17 MED21 ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_8

... is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator ... Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C ... "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, ... Cyclin-dependent kinase inhibitor 1C has been shown to interact with: LIMK1, MYBL2, MyoD, and PCNA. ENSG00000129757 GRCh38: ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_inhibitor_1C

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 ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase

November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... 40 (6): 642-51. doi:10.1136/jcp.40.6.642. PMC 1141055. PMID 3497180. Berger F, Felman P, Thieblemont C, et al. (March 2000). " ...

https://en.wikipedia.org/wiki/Splenic_marginal_zone_lymphoma

... 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, ... Fåhraeus R, Laín S, Ball KL, Lane DP (1998). "Characterization of the cyclin-dependent kinase inhibitory domain of the INK4 ...

https://en.wikipedia.org/wiki/CDKN2C

Additionally, cyclin-dependent kinase (CDK) 4/6 inhibition has shown to improve the efficacy of endocrine treatment. Bray, ... For example, the ER can promote transcription of cyclin D1, an important regulator of the cell cycle. By interfering with the ... The signaling pathways associated with the GPER protein involve tyrosine kinases (from the Src family). Additionally, there is ... 68 (6): 398. doi:10.3322/caac.21492. "Breast cancer in women". nhs.uk. 2017-10-20. Retrieved 2021-10-06. Akram, Muhammad; Iqbal ...

https://en.wikipedia.org/wiki/Endocrine_therapy_resistance_in_breast_cancer

Malumbres M, Ortega S, Barbacid M. «Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.» Biol Chem ... Toll-like Receptor-4 (TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol ... Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6." (2011) His scientific career has been awarded with prizes such ... "Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors." (2000). "Toll-like Receptor-4 (TLR4) Down- ...

https://en.wikipedia.org/wiki/Mariano_Barbacid

In eukaryotes, cyclin-dependent protein kinases interact with cyclins to regulate cell cycle progression, and are required for ... the cyclin-dependent kinase regulatory subunit family is a family of proteins consisting of the regulatory subunits of cyclin- ... Six kinase units can be modelled to bind the hexameric structure, which may thus act as a hub for cyclin-dependent protein ... The proteins bind to a regulatory subunit, cyclin-dependent kinase regulatory subunit (CKS), which is essential for their ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_regulatory_subunit_family

There is evidence to suggest that miR-129 directly targets Cdk6, cyclin dependant kinase 6- a cell proliferation regulator. ... 2004). "Cell cycle-dependent transcriptional regulation of calmodulin-binding transcription activator 1 in neuroblastoma cells ... 24 (6): 1407-12. doi:10.3892/ijo.24.6.1407 (inactive 31 July 2022). PMID 15138581.{{cite journal}}: CS1 maint: DOI inactive as ... doi:10.1016/S0960-9822(02)00809-6. hdl:11858/00-001M-0000-0010-94EF-7. PMID 12007417. S2CID 7901788. Lagos-Quintana M, Rauhut R ...

https://en.wikipedia.org/wiki/Mir-129_microRNA_precursor_family

Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by ... For this reason, the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose ... Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of ... By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as ...

https://en.wikipedia.org/wiki/Chemotherapy

Ishimi Y, Komamura-Kohno Y (2001). "Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4, ... This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase ... The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. ... A role for cdc2 kinase". J. Biol. Chem. 273 (27): 17095-101. doi:10.1074/jbc.273.27.17095. PMID 9642275. You Z, Komamura Y, ...

https://en.wikipedia.org/wiki/MCM4

p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ... The prolonged DDR activates both ATM and ATR DNA damage kinases. The phosphorylation cascade initiated by these two kinases ...

https://en.wikipedia.org/wiki/Cellular_senescence

Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors". ...

https://en.wikipedia.org/wiki/Protein_crystallization

... abemaciclib inhibits the enzymes cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). These enzymes are ... This result suggests that there may be a mechanism of action other than inhibition of a cyclin-dependent kinase. After oral ... 111 (6): 2132-2145. doi:10.1111/cas.14419. PMC 7293084. PMID 32304130. LY2835219 Shows Strong Single-Agent Activity in ... a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast ...

https://en.wikipedia.org/wiki/Abemaciclib

... along with mRNA Decay of Cyclin-dependent Kinase 6 Gene". International Journal of Molecular Sciences. 19 (12): 3828. doi: ... 8 (6): R173. doi:10.1186/ar2082. PMC 1794517. PMID 17109745. Saranya Revathy K, Umasuthan N, Whang I, Lee Y, Lee S, Oh MJ, Jung ... 122 (6): 957-68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923. "BoxShade ... 4 (6): 1633-49. doi:10.1002/pmic.200300771. PMID 15174133. S2CID 18810164. Gupta, R (2001). "Prediction of glycosylation sites ...

https://en.wikipedia.org/wiki/SAAL1

... may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a ... Protein kinase inhibitors, Chemotherapeutic adjuvants, Pyridines, Piperazines, Spiro compounds, Amides, Guanidines, All stub ... a CDK 4/6 Inhibitor, in Extensive Stage Small Cell Lung Cancer (SCLC)" at ClinicalTrials.gov Clinical trial number NCT02499770 ... a CDK 4/6 Inhibitor, in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy" at ...

https://en.wikipedia.org/wiki/Trilaciclib

... increases proliferation via cyclin-dependent kinases". The Journal of Biological Chemistry. 284 (36): 24223-32. doi:10.1074/jbc ... and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3's synthesis of F2,6BP in the nucleus was found ... Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. The four ... due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. The high '2-Kase' activity of PFKFB3 is also due to ...

https://en.wikipedia.org/wiki/PFKFB3

... has been shown to interact with: AKAP8, CDC2L1, CDKN1B, CRABP2, Cyclin-dependent kinase 4, Cyclin-dependent kinase 6 ... Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Exp. Hematol. ... Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Mol. Cell. Biol. 19 (1): 353- ...

https://en.wikipedia.org/wiki/Cyclin_D3

... has also been shown to directly inhibits CDK6 (Cyclin-dependent kinase 6) expression and decreases the level of ... Voltage-dependent L-type calcium channel subunit beta-2), TSSK6 (Testis-Specific Serine Kinase 6), NT5DC2 (Cytosolic 5'- ... It was observed that miR-137 expression is lost in Ras-dependent pancreatic cancer, and that restoration of its expression ... Serine/threonine-protein kinase D3). Neault et al. recently identified miR-137 as a senescence effector miRNA induced by ...

https://en.wikipedia.org/wiki/MiR-137

Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ... Ribociclib is a kinase inhibitor indicated in combination with: an aromatase inhibitor for the treatment of pre/perimenopausal ... Ribociclib, sold under the brand name Kisqali and Kryxana marketed by Novartis, is an inhibitor of cyclin D1/CDK4 and CDK6, and ... Protein kinase inhibitors, Carboxamides, Pyridines, Novartis brands, Pyrimidines, Piperazines, Cyclopentanes). ...

https://en.wikipedia.org/wiki/Ribociclib

... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... 1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)". Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...

https://en.wikipedia.org/wiki/P21

Biochemical triggers known as cyclin-dependent kinases (Cdks) switch on cell cycles events at the corrected time and in the ... During G1 phase, the G1/S cyclin activity rises significantly near the end of the G1 phase. Complexes of cyclin that are active ... which targets and degrades S and M cyclins (but not G1/S cyclins); and a high concentration of Cdk inhibitors is found during ... At the G1/S checkpoint, formation of the G1/S cyclin with Cdk to form a complex commits the cell to a new division cycle. These ...

https://en.wikipedia.org/wiki/G1_phase

Zhu D, Dix DJ, Eddy EM (August 1997). "HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes". ... as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. ... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... where it is necessary for the formation of the complex between CDC2 and cyclin B1. It later becomes incorporated into the ...

https://en.wikipedia.org/wiki/HSPA1B

Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ... Nigg EA (June 1995). "Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle". BioEssays. 17 (6): 471-80 ... October 2003). "Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859-64. Bibcode:2003Natur.425..859U. doi: ...

https://en.wikipedia.org/wiki/Cell_cycle

15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ... DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular ... Cyclin D1, Cdk4, and Insulin-like growth factor 1; and e) regulating agents such as HSP70, GPR78, Gadd153, Ubiquitin B, and ... It (they) regulates signaling by: a) inhibiting the STAT3-Janus kinase pathway to block cellular pro-inflammatory responses; b ...

https://en.wikipedia.org/wiki/Cyclopentenone_prostaglandins

"The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... p21 p53 Cyclin-dependent kinase Cyclin D GRCh38: Ensembl release 89: ENSG00000147889 - Ensembl, May 2017 GRCm38: Ensembl ... "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". Nobori T, Miura K, Wu DJ, Lois A, ... p16 is an inhibitor of cyclin-dependent kinases (CDK). It slows down the cell cycle by prohibiting progression from G1 phase to ...

https://en.wikipedia.org/wiki/P16

7SK associates with and inhibits the cyclin dependent kinase activity of P-TEFb through the action of the RNA binding proteins ... Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA ... Yang Z, Zhu Q, Luo K, Zhou Q (November 2001). "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control ... July 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Molecular and ...

https://en.wikipedia.org/wiki/7SK_RNA

"Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase". Molecular and Cellular Biology. 23 (5): 1764 ... For example, Hsc70 regulates the nuclear accumulation of cyclin D1, which is a key player in G1 to S phase cell cycle ... Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 62 (6): 670-684. doi:10.1007/s00018-004-4464-6. PMC 2773841. PMID 15770419. Wang X, Wang Q, Lin H, Li S, Sun L, Yang Y (Feb ...

https://en.wikipedia.org/wiki/HSPA8

Hennigan RF, Stambrook PJ (August 2001). "Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase ... AP-1 functions are heavily dependent on the specific Fos and Jun subunits contributing to AP-1 dimers. The outcome of AP-1 ... Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... Manicassamy S, Gupta S, Huang Z, Sun Z (June 2006). "Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up ...

https://en.wikipedia.org/wiki/AP-1_transcription_factor

... phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other ... Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2)". J. Biol. Chem. 276 (49): 45780-90. doi: ... attachment region upstream of the T cell receptor beta gene enhancer binds Cux/CDP and SATB1 and modulates enhancer-dependent ... phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, ...

https://en.wikipedia.org/wiki/CUTL1

Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase ( ... The singular archaeal ORC protein recognizes the AT-rich tracts and binds DNA in an ATP-dependent fashion. Eukaryotes typically ... "DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1". EMBO Reports. 7 (11): 1134- ...

https://en.wikipedia.org/wiki/Pre-replication_complex

"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ... 6: 175. doi:10.1186/1471-2334-6-175. PMC 1713240. PMID 17166282. v t e (Genes on human chromosome 14, All stub articles, Human ... "Identification of a novel gene family that includes the interferon-inducible human genes 6-16 and ISG12". BMC Genomics. 5 (1): ...

https://en.wikipedia.org/wiki/IFI27

... using cyclins and other proteins. As TFIIB has a similar structure to cyclin A it has been suggested that depleted levels of ... It has been suggested that the general transcription factor TFIIH could act as the kinase for this phosphorylation although ... "New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor ... This is thought to be due to similarity TFIIB has to cyclin A. In order to undergo replication, viruses often stop host cells ...

https://en.wikipedia.org/wiki/Transcription_factor_II_B

... in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events ... Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439-52. doi:10.1016/j.jgg ... Mediator can be divided into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. Mediator ... Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis". Crit Rev Biochem Mol Biol. 50 (5): ...

https://en.wikipedia.org/wiki/Mediator_(coactivator)

... which is required for the function of metaphase cyclin-dependent kinases (M-Cdks). In essence, Activation of the Anaphase- ... Metaphase ends with the destruction of B cyclin. B cyclin is marked with ubiquitin which flags it for destruction by ... Hickson GR, Echard A, O'Farrell PH (February 2006). "Rho-kinase controls cell shape changes during cytokinesis". Current ... promoting complex (APC) causes the APC to cleave the M-phase cyclin and the inhibitory protein securin which activates the ...

https://en.wikipedia.org/wiki/Anaphase

... a well-studied cyclin-dependent protein kinase. Cdc14 antagonizes Cdk1 by stimulating proteolysis of its cyclin partner (cyclin ... It is possible that Cdc14 acts as a phosphatase on all Clb-Cdk1 targets, acting to reverse the effects of the mitotic cyclins. ... April 1999). "Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT ... Furthermore, Cdc14 dephosphorylates the stoichiometric inhibitor of the mitotic cyclins, Sic1, stabilizing Sic1 protein. Cdc14 ...

https://en.wikipedia.org/wiki/Cdc14

... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene. The protein encoded by this ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)". Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai ...

https://en.wikipedia.org/wiki/CDK5R2

TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a ... c-Jun N-terminal kinase (JNK) is a MAP kinase activated by extracellular stress signals such as gamma-radiation, ultraviolet ... EVI1 does not bind other MAP kinases such as p38 or ERK. Among the many other observed defects, EVI1−/− mouse embryos have been ... Together, these two systems disrupt tyrosine kinase signaling and hematopoietic gene transcription. Despite the extensively ...

https://en.wikipedia.org/wiki/MECOM

... it travels to the nucleus via phosphorylation at the Thr-108 position via the mitogenic cyclin dependent kinase (CDK2).[ ... interacts with kinases including serine/threonine protein kinase (PKR). Further studies will need to be performed to better ... E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein ... This includes presence of cytoplasmic vacuoles, double-membrane vesicles, and a dose-dependent decrease in ATP levels. Melanoma ...

https://en.wikipedia.org/wiki/Anticancer_gene

SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclins E/D, respectively, ... This is achieved by continuous control of cyclins or CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ... Moreover, ubiquitination can also act to turn on/off the kinase activity of a protein. The critical role of phosphorylation is ...

https://en.wikipedia.org/wiki/Ubiquitin

"Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis". Nature. 560 (7717): 192-197. Bibcode:2018Natur.560.. ... 100 (6): 533-7. doi:10.1016/j.trstmh.2005.08.018. PMID 16325874. Sundar S, Maurya R, Singh RK, et al. (January 2006). "Rapid, ... 92 (6): 2626-32. doi:10.1172/JCI116878. PMC 288459. PMID 8254019. Holaday B (2000). "Role of CD8+ T Cells in Endogenous ... 6 (6): CD009135. doi:10.1002/14651858.CD009135.pub2. PMC 4468926. PMID 24947503. Chappuis F, Rijal S, Soto A, Menten J, ...

https://en.wikipedia.org/wiki/Visceral_leishmaniasis

"Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors". J. ... Alvocidib (INN; also known as flavopiridol) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development by Tolero ... Protein kinase inhibitors, Orphan drugs, All stub articles, Antineoplastic and immunomodulating drug stubs). ... 100 (6): 659-65. doi:10.1161/01.cir.100.6.659. PMID 10441105. Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, ...

https://en.wikipedia.org/wiki/Alvocidib

This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent ... kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs ... Serine/threonine-protein kinase PRP4 homolog is an enzyme that in humans is encoded by the PRPF4B gene. Pre-mRNA splicing ... 2002). "Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes ...

https://en.wikipedia.org/wiki/PRPF4B

Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 ... βTRCP recognizes these substrates after they are phosphorylated by Polo-like kinase 1 or Cyclin B-CDK1. Fbw7, which is the ... Schwob, E (1994-10-21). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae". Cell. 79 ... SCF-fbxo4 plays a role in cell cycle control by targeting cyclin D1 for degradation. Cyclin F is an FBP that is associated with ...

https://en.wikipedia.org/wiki/SCF_complex

Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to ... The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at ... Chk1 is an effector protein kinase that maintains mitotic cyclin in an inactive state and is phosphorylated by rad3 between S ... pathways which activate the Chk2 and Chk1 kinases, respectively. These kinases act upstream of Cdc25 and Wee1, the direct ...

https://en.wikipedia.org/wiki/G2-M_DNA_damage_checkpoint

Tyrosine kinases are enzymes that add phosphates to tyrosine residues, and are the opposing enzymes to PTPs. PTPs are known to ... cyclin D1 and c-myc. Expression of ful-length PTPkappa in melanoma cells that normally lack its expression results in reduced ... soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent ... "Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases". Genome Biol. 7 (1): R5. doi: ...

https://en.wikipedia.org/wiki/PTPRK

... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... A dose-dependent response was not observed, raising questions about the robustness of the findings. Genes,+tat at the US ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA. Tat protein also associates with ...

https://en.wikipedia.org/wiki/Tat_(HIV)

... such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45α, as well as the transcription factor c-myc, which is directly controlled by ... This PER/CRY complex moves into the nucleus upon phosphorylation by CK1-epsilon (casein kinase 1 epsilon) and inhibits the CLK/ ... Ceriani MF, Darlington TK, Staknis D, Más P, Petti AA, Weitz CJ, Kay SA (July 1999). "Light-dependent sequestration of TIMELESS ... Hao H, Allen DL, Hardin PE (July 1997). "A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster". ...

https://en.wikipedia.org/wiki/Period_(gene)

The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...

https://en.wikipedia.org/wiki/DNA_repair

HR+/HER2- Metastatic Breast Cancer: What Can You Do to Optimize Patient Access to Cyclin-dependent Kinase 4 and 6 Inhibitors ... Assess the designs of- and results from real-world studies on CDK4/6 inhibitors for the management of patients with HR+/HER2- ... Evaluate the designs of- and results from clinical trials assessing the safety and efficacy of CDK4/6 inhibitors for the ... This live virtual TeleECHO educational series targets healthcare gaps related to the familiarity and understanding of CDK4/6 ...

https://www.medlearninggroup.com/cme-programming/mbc-echo1/

And two drug classes on the list, cyclin-dependent kinase 4 and 6 (CDK 4 and CDK 6) inhibitors, showed potential links with ... Cyclin-dependent kinase 4 and 6 (CDK 4 and CDK 6) inhibitors ...

https://www.medscape.com/viewarticle/924040

102000003903 Cyclin-Dependent Kinases Human genes 0.000 description 2 * 108090000266 Cyclin-Dependent Kinases Proteins 0.000 ... 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1 * 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 ... as inhibitors of cyclin dependent kinases, (in particular, cyclin dependent kinases selected from CDK1, CDK2, CDK3, CDK4, CDK5 ... 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 2 * 108010014905 Glycogen Synthase Kinase 3 Proteins ...

https://patents.google.com/patent/US10799506/en

Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646.500]. *Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.646. ... Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21. ... "Cyclin-Dependent Kinase 2" by people in Harvard Catalyst Profiles by year, and whether "Cyclin-Dependent Kinase 2" was a major ... Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.200.323]. *Proline-Directed Protein Kinases [D08.811.913.696.620.682. ...

https://connects.catalyst.harvard.edu/Profiles/display/Concept/Cyclin-Dependent%20Kinase%202

... gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb ... gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53- ... These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by ... We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot ...

https://greenmedinfo.com/article/gingerol-may-help-combat-chemotherapy-resistant-pancreatic-cancer-cells

One example is the closely related cyclin-dependent kinases 4 and 6 (CDK4/6). ... While most kinase research has tended to focus on characterizing phosphorylation networks between kinases and their substrates ... of all human kinases and more than 24% of all substrates. Convergence is also widespread when more than one kinase is ... more than 500 kinases phosphorylate approximately 15% of all proteins. However, more than one kinase can phosphorylate the same ...

https://www.sflorg.com/2023/03/med03202301.html

... this risk to the prescribing information and Patient Package Insert for the entire class of these cyclin-dependent kinase 4/6 ( ... Palbociclib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that ... CDK 4/6 inhibitors have been shown to improve the amount of time after the start of treatment the cancer does not grow ... CDK 4/6 inhibitors block certain molecules involved in promoting the growth of cancer cells. FDA approved palbociclib in 2015, ...

https://medlineplus.gov/druginfo/meds/a615013.html

Cyclin-Dependent Kinase 6 Is a Chromatin-Bound Cofactor for NF-κB-Dependent Gene Expression. Mol. Cell. [Epub ahead of print]. ... Interrogating cAMP-dependent kinase signaling in Jurkat T-Cells by a protein kinase A targeted immune-precipitation ... Phosphoproteomics Analysis Identifies Novel Candidate Substrates of the Nonreceptor Tyrosine Kinase, rc-elated Kinase Lacking C ... Kinase Phosphatase-5-regulated MAP Kinase Target in Interleukin 6 (IL-6) Secretion and Myogenesis. J Biol Chem.. 2017;292(9): ...

https://www.cellsignal.com/learn-and-support/publications-and-posters/proteomics-case-study-publication?N=102285+4294956305&Nrpp=100&No=%257Boffset%257D&fromPage=plp

Cyclin D interacts directly with cyclin-dependent kinases 4 and 6 (CDK4/6) in an active protein complex that promotes cell ... A Phase II Trial of Neoadjuvant PD 0332991, a Cyclin-Dependent Kinase (Cdk) 4/6 Inhibitor, in Combination With Anastrozole in ... in combination with a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary objective is to evaluate the progression free ... Many hormone receptor positive breast cancers demonstrate overexpression of cyclin D. ...

https://www.mayo.edu/research/clinical-trials/faculty-search-results?authid=12369616

It targets two specific kinases, or enzymes, that help tumor cells grow and divide. ... Palbociclib was the first CDK 4/6 inhibitor to be approved for breast cancer by the FDA. ... It is a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, which means it targets two specific kinases, or proteins, that help ... Cyclin-dependent kinases 4 and 6 are two proteins that help some breast cancers to grow. Medicines like palbociclib are called ...

https://www.lbbc.org/about-breast-cancer/treatments/targeted-therapy/for-hormone-receptor-positive/palbociclib

ABBREVIATIONS: ACTB: actin, beta; CCND3: cyclin 3; CDK6: cyclin-dependent kinase 6; CHQ: chloroquine; COL4A1: collagen, type IV ... kinase insert domain protein receptor; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MKI67: antigen identified ... ribosomal protein S6 kinase, polypeptide 1; SQSTM1/p62: sequestome 1; TUBB: tubulin, beta; VCL: vinculin; VEGFA: vascular ... When last tested, the vision in the affected eye was excellent in 4 of the 6 patients. The 2 patients without recurrences of ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:V%C3%ADtreo+Prim%C3%A1rio+Hiperpl%C3%A1sico+Persistente/patologia

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have more recently become an important component of the management of this ... Therapy After Cyclin-Dependent Kinase Inhibition in Metastatic Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms ... retinoblastoma protein(pRb), bypass signaling through other cyclin/CDK complexes and activation of upstream signaling pathways ... Beyond CDK4/6 Inhibitors: What Subsequent Treatment Is Best? Beyond CDK4/6 Inhibitors: What Subsequent Treatment Is Best?. ...

https://her2support.org/vbulletin/showthread.php?t=68715

2. Finn RS, Crown JP, Lang I, et al: The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus ... and Pfizer identified a unique role for cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in estrogen receptor (ER)-positive ... 1. Finn RS, Dering J, Conklin D, et al: PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits ... All three CDK4/6 inhibitors cause the "on-target" effect of neutropenia, to some degree, but each differs somewhat in its ...

https://ascopost.com/issues/july-25-2022/changing-the-natural-history-of-er-positive-her2-negative-breast-cancer-with-the-introduction-of-cdk46-inhibition/

It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. ... It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.. ... Cyclin-Dependent Kinase 6 - Preferred Concept UI. M0228003. Scope note. Cyclin-dependent kinase 6 associates with CYCLIN D and ... Cyclin-Dependent Kinase 6 Entry term(s). CDK6 Protein Cdk6 Protein Kinase Cell Division Protein Kinase 6 Cyclin Dependent ...

https://decs.bvsalud.org/en/ths/resource/?id=50716

Targeting cyclin-dependent kinase 4 (CDK4) and CDK6 increases endocrine therapy efficacy, leading to the approval of CDK4/6 ... 6% (84·8-92·5) for those with an inadequate response who received radiotherapy. ...

https://www.thelancet.com/latest-news-comment?SeriesKey=eclinm&SeriesKey=langlo&SeriesKey=lanchi&SeriesKey=ebiom&rel=nofollow&startPage=&SeriesKey=lanonc

Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors.. Prior cytotoxic chemotherapy for ...

https://www.survivornet.com/clinical-trials/prostate-cancer/a-study-of-abiraterone-acetate-plus-prednisone-with-or-without-abemaciclib-ly2835219-in-participants-with-prostate-cancer/

... cyclin-dependent kinase 4/6; DCIS; ductal carcinoma in situ; DFS; disease-free survival; ER; estrogen receptor; FDA; Food and ... Aurora kinase A; AURKB; Aurora kinase B; BCS; Biopharmaceuti ... Cyclin D1 and PPARÎ³; CBD; Cannabidiol; ER; Estrogen receptor; ... Keywords: سرطان سینه سه گانه منفی; Sphingosine-1-phosphate; Sphingosine kinase; Estradiol; Breast cancer; FTY720/Fingolimod; ... extracellular signal regulated kinase; E2; 17Î²-estradiol; H ... دانلود رایگان متن کامل مقاله ISI 6 صفحه سال انتشار : 2018 سفارش ...

https://daneshyari.com/isi/articles/triple_negative_breast_cancer

Abstract 16720: Cardiovascular Toxicities of Cyclin Dependent Kinase (cdk) 4/6 Inhibitors in Metastatic Breast Cancer Patients ... ABT-702, an adenosine kinase inhibitor, attenuates inflammation in diabetic retinopathy. Elsherbiny, N. M., Ahmad, S., Naime, M ... Acadesine inhibits tissue factor induction and thrombus formation by activating the phosphoinositide 3-kinase/akt signaling ... Buckley, P. F., Cannon, M. & Larkin, C., Jan 1 1991, In: British Journal of Addiction. 86, 6, p. 789-790 2 p.. Research output ...

https://augusta.elsevierpure.com/en/publications/?showAdvanced=false&allConcepts=true&inferConcepts=true&publicationYear=2011&publicationYear=2012&publicationYear=2013&publicationYear=2014&publicationYear=2015&publicationYear=2017&format=&ordering=title&descending=false&nofollow=true&page=9

Palbociclib works by blocking proteins called cyclin-dependent kinase 4 and 6, which regulate cell growth and division. ... Palbociclib works by blocking proteins called cyclin-dependent kinase 4 and 6, which regulate cell growth and division. ... If you are allergic to Palbociclib or any of the other ingredients of this medicine (listed in section 6). ...

https://acteropharma.com/product/ibract/

7. Takatsuka H, Umeda-Hara C, Umeda M (2015) Cyclin-dependent kinase-activating kinases CDKD;1 and CDKD;3 are essential for ... 2008) Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic ... 2012) Genetic framework of cyclin-dependent kinase function in Arabidopsis. Dev Cell 22: 1030-1040. doi: 10.1016/j.devcel. ... Článek Aurora kinase A is essential for meiosis in mouse oocytes Článek Pathways and signatures of mutagenesis at targeted DNA ...

https://www.prolekare.cz/casopisy/plos-genetics/2021-4-28/the-canonical-snap-is-essential-for-gametophytic-development-in-arabidopsis-132689

Genetic Association of rs2237572 Cyclin-Dependent Kinase 6 Gene with Breast Cancer in Iraq. Indian journal of clinical ...

https://phgkb.cdc.gov/PHGKB/searchSummary.action?firstQuery=Breast+Neoplasms+and+CDK6&Mysubmit=Search

1 cyclin dependent kinase (CDK) 4/6 inhibitors have been a heavily-researched and discussed class of medication for ... Cyclin dependent kinase (CDK) 4/6 inhibitors are the latest addition to this arsenal of therapies, and while they have been ... Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res. 2016;18:17. ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. ...

https://touchoncology.com/breast-cancer/journal-articles/why-cdk-4-6-inhibitors-are-practice-changing-in-advanced-breast-cancer/

This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ...

https://okayama.elsevierpure.com/en/publications/cyclin-dependent-kinase-like-5-binds-and-phosphorylates-dna-methy

Cyclins and cyclin-dependent kinases. Cyclins and cyclin-dependent kinases (CDKs) are involved in cell-cycle regulation. The ... phosphatidylinositol-3-kinase; Akt, protein kinase B; mTOR, mammalian target of rapamycin; CDK, cyclin-dependent kinase) ... Cyclin D1 activates cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), thus inactivating the retinoblastoma tumour suppressor ... The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line ...

https://www.amsj.org/archives/4769

A recent multicenter randomized trial showed that the addition of the investigational cyclin-dependent kinase (CDK) 4/6 ... cyclin D1, regulate cell-cycle progression. CDK4/6 overexpression and amplification of cyclin D1 gene occur frequently in HR- ... The efficacy of anti-CDK 4/6 therapy in advanced HR-positive breast cancer was demonstrated at the 2016 ASCO annual meeting in ... Hortobagyi reported findings from the MONALEESA-2 trial, a first-ever phase III study of a CDK 4/6 inhibitor and an endocrine ...

https://www.oncnursingnews.com/view/ribociclib-reduces-progression-of-hr-positive-metastatic-breast-cancer

Regulation of protein phosphatase inhibitor-1 by cyclin-dependent kinase 5.. J Biol Chem. 282(22):16511-20.*PubMed ...

https://anesthesiology.weill.cornell.edu/research/publications?page=5&%3Bf%5Bauthor%5D=2191&s=year&o=desc&f%5Bauthor%5D=633

Informations about Cyclin Dependent Kinase Inhibitor 2D (CDKN2D) Antibody (abx005030-20) ... The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been ... The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression ... shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth ...

https://www.hoelzel-biotech.com/en/antibody-abx005030-20-cyclin-dependent-kinase-inhibitor-2d-cdkn2d-antibody.html

For premenopausal women diagnosed with hormone receptor (HR)-positive, HER2-negative BC, cyclin-dependent kinase 4 and 6 (CDK4/ ... Currently, ribociclib is the only CDK4/6 inhibitor studied in the first-line setting for premenopausal women with HR+/HER2- aBC ...

https://specialty.mims.com/labor%20induction/treatment

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are oral targeted therapies that block a protein called cyclin-dependent kinase ... The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in patients with ... Approximately 40% of lobular tumors harbor a PI3 Kinase (PIK3CA) mutation, for which there is an approved targeted treatment: ... 2021 Jan 6;19(1):77-102. PMID: 33406487.. 22 Corso G, Figueiredo J, La Vecchia C, Veronesi P, Pravettoni G, Macis D, Karam R, ...

https://lobularbreastcancer.org/faq/

Premenopausal women with breast cancer who receive palbociclib - a cyclin-dependent kinase (CDK) 4/6 inhibitor - combined with ...

https://www.cancertherapyadvisor.com/home/cancer-topics/breast-cancer/palbociclib-plus-fulvestrant-improves-pfs-among-premenopausal-patients-with-breast-cancer/

The aim of this article is to give a short overview of the existing efficacy data, to summarize the recommended clinical monitoring procedures for patients under CDK4/6 inhibitors, and to shed light on the clinical management of the most common treatment-emergent adverse events. (nih.gov)
This live virtual TeleECHO educational series targets healthcare gaps related to the familiarity and understanding of CDK4/6 inhibitor clinical trial designs and results on efficacy, safety, and real-world studies, impacting outcomes through current practice patterns and treatment strategies in the management of HR+/HER2- metastatic breast cancer (mBC). (medlearninggroup.com)
You will also be immersed in interactive, animated simulation case studies to memorably highlight key points related to the mechanism of action of CDK4/6 inhibitors and their related safety profiles. (medlearninggroup.com)
Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition. (nih.gov)
Applying this platform in melanoma cell lines to profile the immunopeptidome response to CDK4/6 inhibition and interferon-γ - known modulators of antigen presentation - uncovers treatment-specific alterations, connecting the intracellular response to extracellular immune presentation. (nih.gov)
1. Approaching Use of CDK4/6 Inhibitors in Metastatic HR+, HER2- Breast Cancer. (nih.gov)
2. Comparative Efficacy of CDK4/6 Inhibitors Plus Aromatase Inhibitors Versus Fulvestrant for the First-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer: A Network Meta-Analysis. (nih.gov)
3. CDK4/6 and PI3K inhibitors: A new promise for patients with HER2-positive breast cancer. (nih.gov)
4. Abemaciclib: a CDK4/6 inhibitor for the treatment of HR+/HER2- advanced breast cancer. (nih.gov)
7. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. (nih.gov)
10. The impact of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) on the incidence of alopecia in patients with metastatic breast cancer (BC). (nih.gov)
11. Targeting CDK4/6 pathways and beyond in breast cancer. (nih.gov)
18. Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial. (nih.gov)
Concurrent inhibition of CDK2 adds to the anti-tumour activity of CDK4/6 inhibition in GIST. (harvard.edu)
Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma. (harvard.edu)
This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. (nih.gov)
One example is the closely related cyclin-dependent kinases 4 and 6 (CDK4/6). (sflorg.com)
Many kinases, particularly cell cycle proteins such as CDK4/6, are drivers of cancer cell proliferation and drug resistance. (sflorg.com)
The researchers took these new insights to dissect the prototypical convergent kinase pair, CDK4/6, which are closely related family members that phosphorylate the retinoblastoma protein (RB) and share overlapping phosphorylation sites. (sflorg.com)
In most contexts, the presence of either CDK4 or CDK6 is sufficient to phosphorylate RB to levels that prohibit analysis of the activity of the other kinase. (sflorg.com)
Also, there are CDK4/6 inhibitors, but not any specific to CDK6 or CDK4 alone, which makes it technically difficult to study them individually. (sflorg.com)
The addition of a CDK4/6 inhibitor that has previously been shown to drive CDK6-mediated inhibitor resistance in breast cancer cells was employed. (sflorg.com)
High-throughput screening identified the imidazo[1,2-a]pyridine and bisanilinopyrimidine series as inhibitors of the cyclin-dependent kinase CDK4. (rcsb.org)
CDK4/6 inhibitors are a class of drugs that target particular enzymes, called CDK4 and CDK6. (drugs.com)
CDK4/6 inhibitors interrupt signals that stimulate the proliferation of malignant (cancerous) cells. (drugs.com)
Certain cancers, for example, hormone receptor-positive breast cancer , are more likely to have disturbances in CDK4/6, and CDK 4/6 inhibitors may form part of the treatment protocol. (drugs.com)
Most often, CDK4/6 inhibitors are given synergistically with hormonal therapy (such as an aromatase inhibitor or fulvestrant), although the CDK4/6 inhibitor abemaciclib may be used alone to treat hormone receptor-positive, HER2-negative metastatic breast cancer in pre-treated patients. (drugs.com)
Research shows CDK4/6 inhibitors increase the time people have before cancer spreads (progression-free survival). (drugs.com)
In general, the side effects associated with CDK4/6 inhibitor therapy are less severe than those experienced with chemotherapy. (drugs.com)
Kevin Kalinsky, MD, MS, spoke about future studies following results from the phase 2 MAINTAIN trial of ribociclib with or without endocrine therapy and after progression on a CDK4/6 inhibitor for patients with unresectable or metastatic hormone receptor-positive, HER2-negative breast cancer. (cancernetwork.com)
Kalinsky also discussed the limitations for single-agent treatment in the post-CDK4/6 setting, and the benefit of the MAINTAIN regimen in this setting. (cancernetwork.com)
If we look at patients after they've had a CDK4/6 inhibitor, giving a single agent hormonal therapy, the median progression-free survival in this study was about 2.76 months [in the placebo arm]. (cancernetwork.com)
The other thing I want to mention just in terms of CDK4/6 inhibitors after a CDK4/6 inhibitor is that it's promising to see that all the observational data and preclinical data, that we've seen is in a randomized trial. (cancernetwork.com)
This is the first proof of principle study demonstrating that there is benefit of CDK4/6 inhibition after CDK4/6 inhibition, and also understanding that we're waiting for other randomized trials. (cancernetwork.com)
When combined with endocrine therapy, which blocks hormone receptors on cancer cells so that they don't grow and multiply uncontrollably, CDK4/6 inhibitors significantly increase progression-free survival, or the time it takes before the cancer spreads further, in women with advanced metastatic breast cancer who are hormone-receptor positive, like Hassen. (everydayhealth.com)
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib or abemaciclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation. (mayo.edu)
SHR6390 (Jiangsu HengRui Medicine) is Cyclin-dependent kinases 4 and 6 (CDK4/6) of cell cycle progression and are dysregulated in cancers. (delveinsight.com)
Inhibition of CDK4/6 induces G1 phase cell cycle arrest, therefore retards tumour growth. (delveinsight.com)
CDK4 and 6 are serine/threonine kinases that are up-regulated in many tumour cell types and play a vital role in the regulation of cell cycle progression. (delveinsight.com)
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have more recently become an important component of the management of this breast cancer subtype, significantly delaying time to the disease progres- sion and improving survival when combined with endocrine therapy. (her2support.org)
As more women receive CDK4/6 inhibitors as part of their treatment, the management of de novo and acquired resistance to combined CDK4/CDK6 inhibitor plus endocrine therapy regimens has emerged as an important clinical chal- lenge. (her2support.org)
Several resistance mechanisms have been described, including alterations in the CDK4/6/cyclin D complex or its major effector retinoblastoma protein(pRb), bypass signaling through other cyclin/CDK complexes and activation of upstream signaling pathways, in particular the PI3K/mTOR pathway, but robust biomarkers to predict resistance remain elusive, and the role for continuing CDK4/6 inhibitors after progression remains under investigation. (her2support.org)
Novel strategies being evaluated in clinical trials include the continuation of CDK4/6 inhibitors through progression, as well as triplet therapy combinations with PI3K inhibitors or immune checkpoint inhibitors. (her2support.org)
Beyond CDK4/6 Inhibitors: What Subsequent Treatment Is Best? (her2support.org)
It has been 14 years since a collaboration between the University of California, Los Angeles (UCLA) and Pfizer identified a unique role for cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in estrogen receptor (ER)-positive human cell line models and demonstrated that these agents act synergistically with agents targeting the ER pathway. (ascopost.com)
1 This work led to the proof-of-concept PALOMA-1 study, which for the first time demonstrated a significant improvement in progression-free survival in postmenopausal women with advanced ER-positive/HER2-negative breast cancer treated with the combination of a CDK4/6 inhibitor-palbociclib-and letrozole vs letrozole alone. (ascopost.com)
They have since been validated in eight phase III randomized, placebo-controlled studies in advanced ER-positive/HER2-negative breast cancer with three different CDK4/6 inhibitors-palbociclib, ribociclib, and abemaciclib-in various lines of therapy and in different patient populations. (ascopost.com)
Although the progression-free survival of the control arms differed slightly from study to study, based on differences in the inclusion/exclusion criteria and study populations, all of them showed remarkably similar magnitudes of benefit, with hazard ratios in the 0.5 range for the combination of endocrine therapy with a CDK4/6 inhibitor vs endocrine therapy alone. (ascopost.com)
All three CDK4/6 inhibitors cause the "on-target" effect of neutropenia, to some degree, but each differs somewhat in its adverse-event profile. (ascopost.com)
This improvement occurred despite a significant number of patients on the control arm receiving a CDK4/6 inhibitor after disease progression on front-line therapy-34.4% in the control arm vs 21.7% in the ribociclib group. (ascopost.com)
MONALEESA-2 is the first of three trials combining CDK4/6 inhibitors with nonsteroidal aromatase inhibitors in the first-line postmenopausal population to report overall survival data. (ascopost.com)

9. Cyclin-dependent kinase inhibition: an opportunity to target protein-protein interactions. (nih.gov)
8. Inhibition of cyclin-dependent kinases 4 and 6 in breast cancer. (nih.gov)
A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. (cancernetwork.com)

5. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. (nih.gov)
Since palbociclib was approved, CDK 4/6 inhibitors have become the recommended first-line treatment for most people with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. (lbbc.org)
Medicines like palbociclib are called CDK 4/6 inhibitors because they block these proteins from signaling cancer cells to multiply, which helps slow the growth or spread of the cancer. (lbbc.org)
Palbociclib is in a class of medications called kinase inhibitors. (medlineplus.gov)

KISQALI FEMARA CO-PACK, a co-packaged product containing ribociclib, a kinase inhibitor, and letrozole, an aromatase inhibitor, is indicated as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (nih.gov)
6. Ribociclib for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer. (nih.gov)

Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (nih.gov)
3. Dual action of the inhibitors of cyclin-dependent kinases: targeting of the cell-cycle progression and activation of wild-type p53 protein. (nih.gov)
It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. (harvard.edu)
From NCBI Gene: The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. (nih.gov)
The assay can be used for a range of purposes such as understanding the effect of protein modulators on CDK6 function, testing engineered versions of the kinase, or studying the effects of mutations that may be involved in driving disease. (sflorg.com)

14. Cyclin-dependent kinase 4/6 inhibitors as first-line treatment for post-menopausal metastatic hormone receptor-positive breast cancer patients: a systematic review and meta-analysis of phase III randomized clinical trials. (nih.gov)

CDK 4/6 inhibitors are a class of prescription medicines that are used in combination with hormone therapies to treat adults with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer that has spread to other parts of the body. (medlineplus.gov)

Kinases are a specific family of proteins that add phosphates to other molecules - a process called phosphorylation, which can change the function of their substrates (target proteins). (sflorg.com)
In humans, more than 500 kinases phosphorylate approximately 15% of all proteins. (sflorg.com)
Understanding the complex kinase network is important, as dysregulation of these proteins can drive disease, such as the survival and spread of cancer cells or their resistance to therapeutics. (sflorg.com)
It is a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, which means it targets two specific kinases, or proteins, that help tumor cells reproduce. (lbbc.org)
Cyclin-dependent kinases 4 and 6 are two proteins that help some breast cancers to grow. (lbbc.org)

Clearer understanding about the markers and drivers of cancer cell proliferation has emerged from research that identifies new opportunities to overcome convergence with complex enzymes, known as kinases. (sflorg.com)

For instance, convergent serine/threonine kinases are co-expressed in more than 70% of the study's analyzed human cell lines. (sflorg.com)

CDK6 over-expression combined with inhibitor treatment resulted in detection of CDK6-dependent RB phosphorylation. (sflorg.com)
Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe ILD and/or pneumonitis. (medlineplus.gov)

6. Cyclin-dependent kinase modulators and cancer therapy. (nih.gov)

Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis. (drugs.com)

6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. (greenmedinfo.com)
Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. (harvard.edu)

The research also identified signaling pathways where reciprocal phosphorylation loops occur, when the substrate of a kinase can phosphorylate that kinase. (sflorg.com)
Phosphoproteomic Analysis of FLCN Inactivation Highlights Differential Kinase Pathways and Regulatory TFEB Phosphoserines. (cellsignal.com)

Cyclin-Dependent Kinase 2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)

2. Investigational drugs targeting cyclin-dependent kinases for the treatment of cancer: an update on recent findings (2013-2016). (nih.gov)

4. Targeting Cyclin-Dependent Kinases and Cell Cycle Progression in Human Cancers. (nih.gov)
8. An insight into the emerging role of cyclin-dependent kinase inhibitors as potential therapeutic agents for the treatment of advanced cancers. (nih.gov)
The requirement for cyclin E in c-Myc overexpressing breast cancers. (harvard.edu)

Interstitial Lung Disease (ILD)/Pneumonitis: Patients treated with CDK 4/6 inhibitors should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. (nih.gov)
the epidemiology and outcome of patients with LM from ER + HER2-ABC thus remain unclear because of the notably poor outcome compared with BM [ 6 - 9 ].Therefore, in the present study, we retrospectively investigated the actual situation of ER + HER2-ABC patients with LM in a single institute. (researchsquare.com)

16. CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases. (nih.gov)

Lehmann et al 9 described 6 discrete subtypes of TNBC based on gene expression profiling: basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR). (jnccn.org)
Genetic Association of rs2237572 Cyclin-Dependent Kinase 6 Gene with Breast Cancer in Iraq. (cdc.gov)

CGP60474 is a potent inhibitor of cyclin-dependent kinase (CDK). (adooq.com)
TG003 is a potent, specific, reversible, and ATP competitive inhibitor of Cdc2 like kinase(Clk). (adooq.com)

It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (nih.gov)
We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. (greenmedinfo.com)

CDK 4/6 inhibitors have been shown to improve the amount of time after the start of treatment the cancer does not grow substantially and the patient is alive, called progression-free survival (See List of FDA-Approved CDK 4/6 Inhibitors below). (medlineplus.gov)
As previously mentioned, the study met its primary endpoint of improving progression-free survival (hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.43-0.72, P = 3.29 × 10 −6 for superiority). (ascopost.com)

However, more than one kinase can phosphorylate the same substrate, and this can occur at the same or different sites. (sflorg.com)

HR+/HER2- Metastatic Breast Cancer: What Can You Do to Optimize Patient Access to Cyclin-dependent Kinase 4 and 6 Inhibitors? (medlearninggroup.com)

11. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. (nih.gov)

13. Cyclin-dependent kinase 4 and 6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer: a meta-analysis of randomized clinical trials. (nih.gov)

Cyclin-dependent kinase (CDK) 4/6 inhibitors have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. (nih.gov)
19. Cyclin-dependent kinase inhibitors for the treatment of chronic lymphocytic leukemia. (nih.gov)
p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. (greenmedinfo.com)

1. Targeting cyclin-dependent kinases in anti-neoplastic therapy. (nih.gov)
15. Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014). (nih.gov)
17. Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG). (nih.gov)

15. Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors confers cross-resistance to other CDK inhibitors but not to chemotherapeutic agents in breast cancer cells. (nih.gov)
These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53- expressing cells by inducing temporal growth arrest. (greenmedinfo.com)

And two drug classes on the list, cyclin-dependent kinase 4 and 6 (CDK 4 and CDK 6) inhibitors, showed potential links with interstitial lung disease/pneumonitis. (medscape.com)

6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. (greenmedinfo.com)
While most kinase research has tended to focus on characterizing phosphorylation networks between kinases and their substrates, researchers in the Janovjak Lab at Flinders University's College of Medicine and Public Health have taken a different tack by analyzing how common convergence is across all human kinases, and using these insights to dissect it experimentally. (sflorg.com)

Controlling cell proliferation by targeting cyclin-dependent kinase 6 using drug repurposing approach. (bvsalud.org)
Cyclin-dependent kinase 6 (CDK6) is an essential kinase in cell cycle progression, which is a viable target for inhibitors in various malignancies , including breast cancer . (bvsalud.org)
13. The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer. (nih.gov)
The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild- type (wt) p53 and BxPC-3 expressing mutated p53. (greenmedinfo.com)
CDK stands for cyclin-dependent kinase, and it is an enzyme that is important for cell division. (drugs.com)

While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. (greenmedinfo.com)

This is known as convergence, and can often make it difficult to study a specific kinase or substrate, as the activity of multiple kinases can hamper analysis. (sflorg.com)
Our aim was to find new avenues to study them more effectively, as well as analyze and dissect convergence across all human kinases," says Christina Gangemi, a research associate at the Flinders Health and Medical Research Institute. (sflorg.com)

Anatomy15

Organisms8

Diseases2

Chemicals and Drugs164

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes48

Disciplines and Occupations1

Information Science3

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/363)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/363)

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. (3/363)

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (4/363)

NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. (5/363)

Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8. (6/363)

Anchorage dependence of mitogen-induced G1 to S transition in primary T lymphocytes. (7/363)

CTLA-4-Mediated inhibition of early events of T cell proliferation. (8/363)

Cyclin-Dependent Kinases

Cyclin-Dependent Kinase 2

Cyclin D1

Cyclin A

Cyclin E

Cyclins

Cyclin-Dependent Kinase 4

Cyclin-Dependent Kinase Inhibitor p27

CDC2-CDC28 Kinases

Cell Cycle

Cyclin-Dependent Kinase Inhibitor p21

Cyclin-Dependent Kinase 5

Cell Cycle Proteins

Cyclin B

Cyclin C

Protein-Serine-Threonine Kinases

CDC2 Protein Kinase

Cyclin D

G1 Phase

Cyclin-Dependent Kinase Inhibitor p16

Cyclin-Dependent Kinase Inhibitor Proteins

Cyclin D3

Cyclin B1

Retinoblastoma Protein

Phosphorylation

Cyclin-Dependent Kinase 6

Cyclin-Dependent Kinase Inhibitor p57

Tumor Suppressor Proteins

S Phase

Protein Kinase Inhibitors

Cyclin D2

Cyclin A1

Microtubule-Associated Proteins

Protein Kinases

Cell Proliferation

Purines

Cell Division

Apoptosis

Proto-Oncogene Proteins

E2F1 Transcription Factor

Cyclin A2

Phosphatidylinositol 3-Kinases

Cyclin G

Cell Line, Tumor

Tumor Cells, Cultured

Tumor Suppressor Protein p53

Mitosis

Cyclin G1

MAP Kinase Signaling System

Transcription Factor DP1

Signal Transduction

Cells, Cultured

Blotting, Western

Enzyme Inhibitors

G2 Phase

E2F Transcription Factors

Transfection

Calcium-Calmodulin-Dependent Protein Kinases

Mutation

Proliferating Cell Nuclear Antigen

Molecular Sequence Data

Cell Line

DNA-Binding Proteins

Carrier Proteins

Nuclear Proteins

Base Sequence

RNA, Messenger

Protein Kinase C

Transcription Factors

src-Family Kinases

Immunohistochemistry

Reverse Transcriptase Polymerase Chain Reaction

DNA Damage

Antineoplastic Agents

Amino Acid Sequence

p38 Mitogen-Activated Protein Kinases

Cyclic AMP-Dependent Protein Kinases

Cyclin B2

Mitogen-Activated Protein Kinase 1

Protein Binding