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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fingerprint Dive into the research topics of The cyclin-dependent kinase inhibitor p21,sup,WAF1/Cip1,/sup, is an antiestrogen-regulated inhibitor of Cdk4 in human breast cancer cells. Together they form a unique fingerprint. ...
Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found mutated in human tumors. We investigated p27 protein expression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transformation and/or progression. We performed immunohistochemistry and Western blot analysis of each specimen. We found that tumors expressing low to undetectable levels of p27 contained high p27 degradation activity. When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times (P = 0.0012).. The possibility of a simple assay, such as the immunohistochemical analysis of p27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of ...
The major findings in this study are that the Kip/Cip and Ink CKIs differentially regulate cdk2 and cdk4 in VSMCs; this, in turn, leads to differences in the inhibition of VSMC proliferation in vitro and in vivo. The expression of p27Kip1 and p21Cip1 in VSMCs inactivated cdk2 and cdk4, whereas p16Ink4 inhibited only cdk4 activity. In vivo, p27Kip1 significantly inhibited intimal cell proliferation and the development of a neointima after vascular injury, whereas p16Ink4 expression did not lead to a reduction in cell proliferation or neointima formation.. This different pattern of CKI inactivation of the CDKs suggests varied biological roles for p27Kip1 and p21Cip1 compared with p16Ink4 in VSMCs. p27Kip1 was initially characterized as an inhibitor of cyclin E/cdk2 phosphorylation.10 11 p27Kip1 and p21Cip1 are upregulated in several animal models of wound repair. p27Kip1 is constitutively expressed in normal arteries, is downregulated after arterial injury, and is upregulated during the later ...
Anti-HER2 antibody trastuzumab is emerging as a frontline therapy for patients with metastatic breast cancers that overexpress HER2. Understanding the molecular mechanisms by which the antibody inhibits tumor growth should permit the design of even more effective trastuzumab-based protocols. Several …
Our research line is made of three sublines, specialized in the investigation of brain pathologies, including cerebrovascular diseases, neurodegenerative diseases, and brain ageing.. ...
To confirm that the accumulation of p53 was due to decreased degradation of the protein rather than elevated expression of the p53 gene, we treated three wild-type p53 cancer cell lines with Nutlin-1 for 8 hours and monitored the expression of the p53 and p21 genes by real-time polymerase chain reaction (PCR) (Fig. 2B). The transcription of p21 increased in a dose-dependent manner in all cell lines consistent with accumulation of its transcriptional activator p53 (Fig. 2A). By contrast, transcription of the p53 gene itself was unaffected by Nutlin-1, even at the highest concentration tested (16 μM), which caused an 8- to 10-fold induction of p21 mRNA. These data indicate that the Nutlins up-regulate p53 by means of a posttranslational mechanism.. One of the main cellular consequences of p53 activation in proliferating cells is cell cycle arrest in G1 and G2 phases. The cyclin-dependent kinase inhibitor p21 plays a major role in this arrest (22). Cell cycle analysis of bromodeoxyuridine ...
2017) Keywords: Biomarkers, Tumor Carcinoma, Squamous Cell Cell Transformation, Viral Cyclin-Dependent Kinase Inhibitor p16 DNA, Viral Humans In Situ Hybridization Neoplasm Proteins Oncogene Proteins, .... ...
Complete information for CDKN1B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 1B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDKN2B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab92741 交差種: Ms,Rat 適用: WB,IHC-P
Cyclin-Dependent Kinase Inhibitor p27: 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.
Cyclin-Dependent Kinase Inhibitor p27: 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.
Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1 (By similarity).
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
MicroRNA-200b and microRNA-200c (miR-200b/c) are 2 of the most frequently upregulated oncomiRs in intestines cancer cells. cell lines. Additionally, we confirmed that dominance of RECK by miR-200b/c therefore brought about SKP2 (S-phase kinase-associated proteins 2) level and g27Kip1 (also known as cyclin-dependent kinase inhibitor 1B) destruction in intestines cancers cells, which promotes cancer cell proliferation […]. Read More ». ...
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Plant S-phase kinase-associated protein 1 (SKP1) genes play crucial roles in plant development and differentiation. However, the role of SKP1 in citrus is unclear. Herein, we described a novel SKP1-like gene, designated as CrWSKP1, from
S-phase kinase-associated protein 2 (424 aa, ~48 kDa) is encoded by the human SKP2 gene. This protein is involved in the regulation of protein-protein interactions that govern the cell cycle.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
cGMP Dependent Kinase Inhibitor Peptide chemical properties, What are the chemical properties of cGMP Dependent Kinase Inhibitor Peptide 82801-73-8, What are the physical properties of cGMP Dependent Kinase Inhibitor Peptide ect.
https://www.databridgemarketresearch.com/toc/?dbmr=global-cell-cycle-inhibitors-market. Competitive Landscape and Global Cell Cycle Inhibitors Market Share Analysis. Cell cycle inhibitors market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, company strengths and weaknesses, product launch, clinical trials pipelines, product approvals, patents, product width and breath, application dominance, technology lifeline curve. The above data points provided are only related to the companies focus related to cell cycle inhibitors market.. Global Cell Cycle Inhibitors Market Country Level Analysis. The countries covered in the cell cycle inhibitors market report are U.S., Canada, Mexico in North America, Brazil, Argentina, Peru, Rest of South America, as part of South America, Germany, ...
Background 14-3-3 is a p53-mediated cell-cycle inhibitor in epithelial cells. those of additional cell-cycle inhibitor genes, CDKN2A and ARF. Results The manifestation levels of 14-3-3 mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3 mRNA was aberrantly overexpressed regularly in mature lymphoid malignancies (30 of 93, 32.3%) and rarely in acute leukemia (3 of 35, 8.6%). 14-3-3 protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3 gene was not associated with manifestation in hematological malignancies. Mutations of p53 were recognized in 12 individuals and associated with lower manifestation of 14-3-3. The manifestation levels of 14-3-3, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is definitely incompatible with tumor growth. ...
Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodula …
Harrison, T.A., Smith Adams, L.B., Moore, P.D., Perna, M.K., Sword, J.D.and Defoe, D. M.. Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1.BMC Neuroscience 2011, 12:34 ...
BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells ...
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
2VTN: Identification of N-(4-Piperidinyl)-4-(2,6-Dichlorobenzoylamino)-1H-Pyrazole-3-Carboxamide (at7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design.
The p57(Kip2) cyclin-dependent kinase inhibitor (CDKi) has been implicated in embryogenesis, stem-cell senescence and pathologies, but little is known of its role in cell cycle control. Here, we show that p57(Kip2) is ...
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These effects are mediated by nuclear accumulation of the p27(Kip1) inhibitor induced by the downregulation of the p45(Skp2) and Cks1 proteins, which target p27(Kip1) for degradation ...
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
Sustained activation of extracellular signal-regulated kinase (ERK) has been detected previously in numerous tumors in the absence of RAS-activating mutations. However, the molecular mechanisms responsible for ERK-unrestrained activity independent of RAS mutations remain unknown. Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a specific inhibitor of ERK, and S-phase kinase-associated protein 2 (SKP2)/CDC28 protein kinase 1b (CKS1) ubiquitin ligase complex in human hepatocellular carcinoma (HCC). Levels of DUSP1, as assessed by real-time reverse transcription-PCR and Western blot analysis, were significantly higher in tumors with better prognosis (as defined by the length of patients survival) when compared with both normal and nontumorous surrounding livers, whereas DUSP1 protein expression sharply declined in all HCC with poorer prognosis. In the latter HCC subtype, DUSP1 inactivation was due to either ...
Mammalian taste buds contain several specialized cell types that coordinately respond to tastants and communicate with sensory nerves. While it has long been appreciated that these cells undergo continual turnover, little is known concerning how adeq
The cyclin-dependent kinase (CDK) inhibitor p27Kip1 has been shown to regulate cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
MicroRNAs (miRNA) have tumor suppressive and oncogenic potential in human cancer, but whether and how miRNAs control cell cycle progression is not understood. To address this question, we carried out a comprehensive analysis of miRNA expression during serum stimulation of quiescent human cells. Time course analyses revealed that four miRNAs are up-regulated and |100 miRNAs are down-regulated, as cells progress beyond the G(1)-S phase transition. We analyzed the function of two up-regulated miRNAs (miR-221 and miR-222) that are both predicted to target the cell growth suppressive cyclin-dependent kinase inhibitors p27 and p57. Our results show that miR-221 and miR-222 both directly target the 3 untranslated regions of p27 and p57 mRNAs to reduce reporter gene expression, as well as diminish p27 and p57 protein levels. Functional studies show that miR-221 and miR-222 prevent quiescence when elevated during growth factor deprivation and induce precocious S-phase entry, thereby triggering cell death. Thus,
Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression in epithelial tumors; however, its role in hematologic malignancies is unknown. Here we demonstrate that TβRIII protein expression is decreased or lost in the majority of human multiple myeloma specimens. Functionally, restoring TβRIII expression in myeloma cells significantly inhibited cell growth, proliferation, and motility, largely independent of its ligand presentation role. In a reciprocal fashion, shRNA-mediated silencing of endogenous TβRIII expression enhanced cell growth, proliferation, and motility. Although apoptosis was not affected, TβRIII inhibited proliferation through induction of the cyclin-dependent kinase inhibitors p21 and p27. TβRIII further regulated myeloma cell ...
Transforming Growth Factor-β (TGF-β) regulates a variety of biological effects, including cellular proliferation, dependent on the cellular context. There is growing evidence that TGF-β regulates numerous pathways independent of Smad, including the PI3K/Akt pathway. Therefore, since FoxO is downstream of PI3K/Akt, we examined the role of TGF-β on the post-translational regulation of FoxO family members. It was found that TGF-β increased the phosphorylation of FoxO1, 3a, and 4, as well as the cytoplasmic localization of FoxO1 in fibroblasts via the PI3K/Akt pathway. In addition, since Akt and FoxO members can induce phosphorylation and transcription of p27ᵏⁱᵖ¹ (a cyclin dependent kinase inhibitor), respectively, we examined both the post-translational and transcriptional regulation of p27ᵏⁱᵖ¹ by TGF-β in fibroblasts. p27ᵏⁱᵖ¹ phosphorylation increased following TGF-β addition, resulting in cytoplasmic localization in fibroblasts over time. p27ᵏⁱᵖ¹ mRNA expression ...
Cyclin-dependent Kinase Inhibitor (CKI); Inhibitor Of Cdc28-Clb Kinase Complexes That Controls G1/S Phase Transition, Preventing Premature S Phase And Ensuring Genomic Integrity; Phosphorylated By Clb5/6-Cdk1 And Cln1/2-Cdk1 Kinase Which Regulate Timing Of Sic1p Degradation; Phosphorylation Targets Sic1p For SCF(CDC4)-dependent Turnover; Functional Homolog Of Mammalian Kip1
CDKN2A / p14ARF antibody (cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)) for ICC/IF, IHC, IHC-Fr, IHC-P, WB. Anti-CDKN2A / p14ARF pAb (GTX23642) is tested in Human samples. 100% Ab-Assurance.
BEZ235 (NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM, respectively. Inhibits ATR with IC50 of 21 nM, whileshown to be a poor inhibitor to Akt and PDK1. Phase 2. ...
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W. Petrich, K.B. Lewandrowski, J.B. Muhlestein, M.E.H. Hammond, J.L. Januzzi, E.L. Lewandrowski, R.R. Pearson, B. Dolenko, J. Fr h, M. Haass, M.M. Hirschl, W. K hler, R. Mischler, J. M cks, J. Ordóñez-Llanos, O. Quarder, R. Somorjai, A. Staib, C. Sylvक़, G. Werner, R. ...
Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin lymphomas that affect the skin. The pathogenesis of these conditions is poorly understood. For example, the signaling mechanisms contributing to the dysregulated growth of the neoplastic T cells are not well defined. Here, we demonstrate that loss of nuclear localization of pro-IL-16 facilitates CTCL cell proliferation by causing a decrease in expression of the cyclin dependent-kinase inhibitor p27Kip1. The decrease in p27Kip1 expression was directly attributable to an increase in expression of S-phase kinase-associated protein 2 (Skp2). Regulation of Skp2 is in part attributed to the nuclear presence of the scaffold protein pro-IL-16. T cells isolated from 11 patients with advanced CTCL, but not those from healthy controls or patients with T cell acute lymphocytic leukemia (T-ALL), demonstrated reduction in nuclear pro-IL-16 levels. Sequence analysis identified the presence of mutations in the 5ι end of the PDZ1 ...
Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP
TBX3, a member of the T-box family of transcription factors, is essential in development and has emerged as an important player in the oncogenic process. TBX3 is overexpressed in several cancers and has been shown to contribute directly to tumour formation, migration and invasion. However, little is known about the molecular basis for its role in development and oncogenesis because there is a paucity of information regarding its target genes. The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, senescence and apoptosis and here we provide a detailed mechanism to show that it is a direct and biologically relevant target of TBX3. Using a combination of luciferase reporter gene assays and in vitro and in vivo binding assays we show that TBX3 directly represses the p21WAF1 promoter by binding a T-element close to its initiator. Furthermore, we show that the TBX3 DNA binding domain is required for the transcriptional repression of p21WAF1
The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) tumor suppressor genes play important roles in the regulation of the cell cycle. The protein products of these two genes, pRB and p16INK4A (p16), respectively, inhibit progression from G1 to S phase. Moreover, p16 has been shown to exert its function through inhibition of CDK4-mediated phosphorylation of pRB. Both genes have been found to be mutated or deleted in a wide range of primary human tumors and tumor cell lines. However, the presence of CDKN2/MTS1 containing nonneoplastic elements in every tumor specimen may contribute to the apparent lower deletion detection rate in resected neoplasms compared to cell lines. We have developed an immunohistochemical assay that allows us to assess p16 expression in formalin-fixed, paraffin-embedded tissues. As controls, we used paraffin-embedded pellets of cell lines with well-defined p16 status (four positive and four negative lines), as well ...
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Background Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (|5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. Principal Findings We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase
We have previously shown that Nodal and ALK7 are expressed in human placenta (Roberts et al., 2003) and that Nodal signalling through ALK7 inhibits trophoblast cell proliferation (Munir et al., 2004), migration and invasion (Nadeem et al., 2011). In this study, we provided evidence that p27 is a key mediator of Nodal signalling in trophoblast cells. We found that Nodal not only upregulated p27 expression, but also induced p27 and CDK2 translocation to the cytoplasm, leading to inhibition of cell proliferation and migration/invasion.. The present study demonstrates that Nodal upregulates p27 mRNA and protein levels through multiple mechanisms. First, we found that in the presence of a transcription inhibitor, Nodal slowed down the decay of p27 mRNA. Second, we observed that Nodal increased p27 levels over a long period of time and this effect was still evident when protein translation was inhibited, suggesting that Nodal increases the p27 protein stability. This notion is further supported by the ...
The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Additionally, studies utilizing a xenograft model shown that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a medical software of miRNAs as therapeutics to target the practical effect of myc on tumor growth. Intro The manifestation and activity of myc transcription element is definitely regularly deregulated in malignancy and attempts to target it have been demanding.1 Myc has an important regulatory part in multiple pathways, including cell cycle,2, 3 rate of metabolism4, 5 and cellular architecture;6, 7 however, its part in the cell cycle is directly related to the proliferative capacity of malignancy cells. The cell proliferative effect of myc can become coupled to changes buy 50-07-7 in levels and activity of the cyclin-dependent kinase inhibitor p27/kip, ENAH ...
ECM accumulation and ASMC proliferation are hallmarks in the development of intimal thickenings associated with the development of atherosclerotic lesions.61 Our recent work has shown that insertion of decorin-overexpressing cells into injured arteries causes a decrease in intimal volume.30 This decrease is due primarily to a decrease in ECM volume rather than a change in cell number within the intima. The results of the present in vitro study support these in vivo observations and, furthermore, suggest that the effects of decorin overexpression may involve the modulation of TGF-β activity.. An initial decrease in DNA synthesis by decorin-overexpressing cells was observed during the first 24 hours after plating, but this relative decrease disappeared at later time points. The relative decrease in LDSN cells of [3H]thymidine incorporation and increase of cyclin-dependent kinase inhibitors p21 and p27 at 24 hours after plating are similar to the effects that were reported in studies of human ...
Synonyms: Regulation of Nuclear Pre-MRNA Domain Containing 1A, RPRD1A, P15RS, Cyclin-Dependent Kinase 2B-Inhibitor-Related Protein, Cyclin-Dependent Kinase Inhibitor 2B-Related Protein (P15INK4B-Related Protein), P15INK4B-Related Protein, HsT3101, Regulation of Nuclear Pre-MRNA Domain-Containing Protein 1A, Cyclin-Dependent Kinase Inhibitor 2B-Related Protein, FLJ10656.. ...
Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.
Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
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Supplementary Materialscancers-12-01563-s001. MHC-I-negative murine tumor cell genes and lines from the IFN- transduction sign pathway are participating. Fhit-transfected tumor cells demonstrated immunogenic extremely, being rejected with a T lymphocyte-mediated immune system response. Strikingly, this immune Vitamin A system rejection was even more regular in females than in men. The immune system response generated secured hosts against the tumor development of non-transfected cells and against various other tumor cells inside our murine tumor PEPCK-C model. Finally, we also noticed a Vitamin A direct relationship between FHIT appearance and HLA-I surface area expression in individual breasts tumors. Recovery of Fhit appearance on MHC course I harmful tumor cells could be a good immunotherapeutic strategy and could even become an individualized immunotherapeutic vaccine. 0.05. A two-tailed Learners 0.05. A two-tailed Learners 0.001, Fisher check) (Body 3A; Body S7A). Small male ...
2vtp: Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design.
https://astx.com/wp-content/uploads/2019/11/logo_white.png 0 0 webadmin https://astx.com/wp-content/uploads/2019/11/logo_white.png webadmin2010-11-29 12:06:482016-11-29 12:06:57Cho et al. 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. Journal of Medicinal Chemistry 53, no. 22 2010: 7938-7957. DOI: 10.1021/jm100571n. ...
Results: In vitro studies showed a pronounced growth inhibitory and pro-apoptotic effect of LBH589 on both HCC cell lines at low micromolar concentrations (IC50 approx. 0.1 µM). Interstingly, the pro-apoptotic effect of Panobinostat was not paralleled by a breakdown of ΔΨm. p53wt HepG2 cells were more sensitive than the p53-/- Hep3B cells. Quantitative PCR and western blotting showed an involvement of the cell cycle regulators p21cip1/waf1 and Chek1 but not the bax/bcl-2 system. Panobinostat regulated the expression of p21cip1/waf1 via a transcriptional upregulation as evidenced by ChIP ...
Dr. Li studies the intracellular pathways related to IL-7s effects on T cell apoptosis and proliferation. She found that IL-7 promotes T cell survival and division by blocking degradation of Mcl-1 and inducing degradation of the cell cycle inhibitor p27kip1. Her current work focuses on identifying the ubiquitination pathways that IL-7 uses to control the stability of Mcl-1
CDKN1C - CDKN1C Mutant (L33R), Myc-DDK-tagged ORF clone of Homo sapiens cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), transcript variant 1 as transfection-ready DNA available for purchase from OriGene - Your Gene Company.
CDKN2A - CDKN2A (untagged)-Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 4 available for purchase from OriGene - Your Gene Company.
Raje N, Hideshima T, Mukherjee S, Raab M, Vallet S, Chhetri S, Cirstea D, Pozzi S, Mitsiades C, Rooney M, Kiziltepe T, Podar K, Okawa Y, Ikeda H, Carrasco R, Richardson PG, Chauhan D, Munshi NC, Sharma S, Parikh H, Chabner B, Scadden D, Anderson KC. Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma. Leukemia. 2009 May; 23(5):961-70 ...
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NU2058 (O6-(Cyclohexylmethyl)guanine) is a potent, competitive and guanine-based CDK inhibitor with IC50s of 17 μM and 26 μM for CDK2 and CDK1. NU2058 has anti-cancer activity. - Mechanism of Action & Protocol.
p21 C/P 1/El and p 2 7K/P 1 are cyclin-dependant kinase inhibitors that fonn an integral part of the cell cycle process. These proteins function as cell-cycle inhibitors, and are able to induce cell cycle arrest by binding ...
Kips Bay Medical Provides Business Update and Reports Second Quarter 2013 Results MINNEAPOLIS--(BUSINESS WIRE)-- Kips Bay Medical, Inc. (NAS: KIPS) , a medical device company focused on
KIP2 deletion affects Bik1 localization at cMT +tips. (A) Bik1 localization in WT (GFP-TUB1) and kip2Δ mutant. In the mutant, Bik1 accumulation is reduced or a
AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM. It is less potent to CDK5/6 and also inhibits GSK3β. Phase 1.Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
SKP2兔多克隆抗体(ab68455)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, ICC实验严格验证,被3篇文献引用并得到1个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
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"Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated ... It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also ... Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... Small molecule inhibitors of the binding site between Skp2 and its substrate p27 have been discovered, and these inhibitors ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... Interleukin 1- and interleukin 2-dependent proliferation of activated T cells, and the activation of quiescent helper T cells ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6 ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51-7. doi:10.1080/10428190210195. PMID ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase inhibitor 1A. External IDs. OMIM: 116899 MGI: 104556 HomoloGene: ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ...
2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Hirai H, Roussel MF, Kato JY, et al. (1995). " ... 1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". ...
... primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression. These regulation ... Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is ... RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then inhibits cofilin, which effectively reorganizes the ... Due to pathophysiological overlap of RhoA and Rho-kinase in asthma, both RhoA and Rho-kinase have become promising new target ...
"Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas". ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... Chiarle, R; Pagano, M; Inghirami, G (2001). "The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes ...
... discovering that the cyclin-dependent kinase inhibitor p27 is critical to OPC development, such that differentiation in ... "Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1". Genes ... Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency (News and Views and ... exploring the role of p27 in oligodendrocyte differentiation, to understand how myelin development occurs. She found that p27 ...
... of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in ... 2 January 2012). "3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179 in IκBα kinase, leading to ... 14 January 2011). "Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen species- and ERK-dependent up ... May 2008). "Flavopiridol suppresses tumor necrosis factor-induced activation of activator protein-1, c-Jun N-terminal kinase, ...
In addition to p53 and Rb, cyclin dependent kinase inhibitors (CKIs), such as p21, p27, and p57, are also important for ... Immunoprecipitation kinase assays revealed that cyclin C has Rb kinase activity. Furthermore, unlike cyclins D and E, cyclin ... co-immunoprecipitation assays revealed that cyclin-dependent kinase 3 (cdk3) promotes G0 exit by forming a complex with cyclin ... Under normal conditions, the yeast cyclin-dependent kinase complex, Pho80-Pho85, inactivates the Pho4 transcription factor ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... See also CDK inhibitor for inhibitors of various CDKs. Interactions[edit]. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
... embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors ( ... CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Cyclins function as activating subunits of enzymatic complex together with cyclin-dependent kinases (CDKs). Different cyclins ... and the Kip/Cip family of CDK-inhibitor proteins. Cyclin-A1 interacts with: CDC20, Cyclin-dependent kinase 2, E2F1, GNB2L1, ... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-157. doi:10.1038/sj.onc.1201252. PMID 9244350. Suzuki Y, Yoshitomo ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... p27−/− knockout phenotype show an overproduction of cells because cyclin D is not inhibited anymore, while p27−/− and cyclin D ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ... Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... Hall M, Peters G (1996). Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Advances ... Cyclins function as regulators of CDKs (Cyclin-dependent kinase). Different cyclins exhibit distinct expression and degradation ... cyclin box domain for cyclin-dependent kinase (CDK) binding and CDK inhibitor binding; LxxLL binding motif for co-activator ...
... proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 ... Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ...
"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... The p27kip1 protein is involved in cell cycle regulation and belongs to the Cip/Kip family of cyclin dependent kinase(CDK) ... inhibitors. These inhibitors possess an N-terminal CDK-inhibitory domain which binds to the ATP binding pocket of the kinase ... This p27 cis-regulatory element is 114 nucleotides in length and is located at the very 5' end of the 5'UTR of the p27 mRNA. It ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... See also CDK inhibitor for inhibitors of various CDKs. Cyclin-dependent kinase 4 has been shown to interact with: CDC37, CDKN1B ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C. ... CDKN2C‏ (Cyclin dependent kinase inhibitor 2C) هوَ بروتين يُشَفر بواسطة جين CDKN2C في الإنسان.[1][2][3] ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ...
... a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation". Molecular ... p27 CDKN1B Schwob E, Böhm T, Mendenhall MD, Nasmyth K (October 1994). "The B-type cyclin kinase inhibitor p40SIC1 controls the ... "The yeast cyclin-dependent kinase inhibitor Sic1 and mammalian p27Kip1 are functional homologues with a structurally conserved ... "In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S ...
They are p15, p16, p18, p19, p21, p27, and p57. Russo AA, Jeffrey PD, Patten AK, Massagué J, Pavletich NP (July 1996). "Crystal ... A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). Several ... Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. They are named by the small letter "p" followed ... Cyclin-Dependent+Kinase+Inhibitor+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH) v t e. ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... CKIs or CIP/KIP family members like the protein p21 and p27 act blocking and inhibiting the assembled C-CDKs binding complex ... Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...
Cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27, binds to and prevents the activation of CyclinE:Cdk2 by ... The G1 phase cyclin-dependent kinase works together with S phase cyclin-dependent kinase targeting p27 for degradation. In turn ... Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein ... Morgan, David O. (November 1997). "CYCLIN-DEPENDENT KINASES: Engines, Clocks, and Microprocessors". Annual Review of Cell and ...
A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus ... CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ...
Like all cyclin family members, cyclin E forms a complex with cyclin-dependent kinase (CDK2). Cyclin E/CDK2 regulates multiple ... The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting ... Cyclin E/CDK2 also phosphorylates p27 and p21 during G1 and S phases, respectively. Smad3, a key mediator of TGF-β pathway ... Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S ...
"Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ... "Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27". The EMBO Journal. 18 (19 ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. doi: ...
"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325 ... Rosner M, Hengstschläger M (November 2004). "Tuberin binds p27 and negatively regulates its interaction with the SCF component ... Cyclin A2 belongs to the cyclin family, whose members regulate cell cycle progression by interacting with CDK kinases. Cyclin ... Wang Y, Prives C (Jul 1995). "Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases ...
... and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/10428190210195 ... "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. ... "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc ...
Whittaker SR, Mallinger A, Workman P, Clarke PA (May 2017). "Inhibitors of cyclin-dependent kinases as cancer therapeutics". ... For example, the retinoblastoma (Rb) and p27 proteins are phosphorylated by Cdk2 - cyclin A/E complexes, fully deactivating ... Cyclin-dependent kinase 2 has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ...
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... or to result from the differential activity of the pro-apoptotic kinase JNK.[89] The ability of proteasome inhibitors to induce ... Assembly of the base complex is facilitated by four assembly chaperones, Hsm3/S5b, Nas2/p27, Rpn14/PAAF1, and Nas6/gankyrin ( ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ...
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. BioEssays. June 1995, 17 (6): 471-80. PMID ... 細胞週期的進行是由不同的週期素(Cyclin)所調控。週期素意味著這些蛋白質的表現量會隨著細胞週期的進行而有所變化,進而確認週期素原來是扮演細胞
... leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G1-phase arrest, as seen in ... Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the ... The first breakthrough in efforts to find a potent, specific, competitive inhibitor of HMG CoA reductase occurred in 1976, when ... Endo, Akira; Kuroda M.; Tsujita Y. (December 1976). "ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis ...
... cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases ( ... Furthermore, triple knockout, p16 addition, and Cdk 4/6 inhibitor addition experiments confirmed that Cyclin D- Cdk 4/6 is the ... Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M, Pagano M, Zhu L (October 2004). "An Rb-Skp2-p27 pathway mediates acute cell ... cyclin E and cyclin A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... CDK-activating kinase. ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... April 2010). "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Res ... Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bas (a Bcl-2 ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ...
... *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... cyclin E, A (Cdk2,1) cyclin A, B, B3 (Cdk1) H. sapiens cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin ... Cyclin A / CDK2 - active in S phase.. *Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 - regulates transition from G1 to ...
The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... Poprzez hamowanie FOXO1 hamuje ekspresję p27 i p21 nasilając ekspresję CDK, co wpływa na promocję wzrostu i podziału komórek. ... Glycogen synthase kinase-3β, NF-κB signaling, and tumorigenesis of human osteosarcoma. „J Natl Cancer Inst". 104 (10), s. 749- ... GSK-3 inhibitor inhibits cell proliferation and induces apoptosis in human osteosarcoma cells. „Oncol Rep". 35 (4), s. 2348-54 ...
de 1993). «The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases». Cell (UNITED STATES) 75 ... de 2003). «CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis» ... de 2002). «Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4». Mol. Cell ... cyclins and cyclin dependent kinases». Oncogene (ENGLAND) 15 (2): 143-57. ISSN 0950-9232. PMID 9244350. doi:10.1038/sj.onc. ...
CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... protein serine/threonine kinase activity. • cyclin-dependent protein serine/threonine kinase activity. ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ...
Rapamycin induces dephosphorylation of 4EBP1 as well, resulting in an increase in p27 and a decrease in cyclin D1 expression. ... They inhibit all of the kinase-dependent functions of mTORC1 and mTORC2 and therefore, block the feedback activation of PI3K/ ... ATP-competitive mTOR kinase inhibitors[edit]. These second generation mTOR inhibitors bind to ATP-binding site in mTOR kinase ... The second generation of mTOR inhibitors is known as ATP-competitive mTOR kinase inhibitors.[7] mTORC1/mTORC2 dual inhibitors ...
"A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer". ... Meanwhile, CDK2 complexes are inhibited by the CIP/KIP proteins such as p21 and p27, When it is time for a cell to enter the ... 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 ...
"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ... September 1993). "Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in ... "Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1". Mammalian ...
... cyclin-dependent kinase inhibitor p27 MeSH D12.776.624.776.355.700 - cyclin-dependent kinase inhibitor p57 See List of MeSH ... cyclin-dependent kinase inhibitor p15 MeSH D12.776.624.776.355.200 - cyclin-dependent kinase inhibitor p16 MeSH D12.776.624.776 ... cyclin-dependent kinase inhibitor p18 MeSH D12.776.624.776.355.400 - cyclin-dependent kinase inhibitor p19 MeSH D12.776.624.776 ... cyclin-dependent kinase 5 MeSH D12.776.167.200.067.900 - cyclin-dependent kinase 9 MeSH D12.776.167.200.580.500 - cdc2 protein ...
They inhibit all of the kinase-dependent functions of mTORC1 and mTORC2 and therefore, block the feedback activation of PI3K/ ... Rapamycin induces dephosphorylation of 4EBP1 as well, resulting in an increase in p27 and a decrease in cyclin D1 expression. ... The second generation of mTOR inhibitors is known as ATP-competitive mTOR kinase inhibitors. mTORC1/mTORC2 dual inhibitors are ... protein tyrosine kinases and protein serine/threonine kinases. Dual-specificity kinases are subclass of the tyrosine kinases. ...
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL ... 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. ... CDK Inhibitor, p27; Cyclin Dependent Kinase Inhibitor 1B; Cyclin Dependent Kinase Inhibitor p27; Kip1 Protein, p27; p27, CDK ...
... most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodula … ... Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase ... Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1) Cell. 1996 May 31;85(5):721-32. doi ... Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase ...
Cyclin-Dependent Kinase Inhibitor p21. *Cyclin-Dependent Kinase Inhibitor p27. *Cyclin-Dependent Kinases/antagonists & ... Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology ... Following IL-6 treatment of LNCaP, Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), ... CDK4, and CDK6 were decreased, while accumulation of CDK inhibitor p27(Kip1) was rapidly and markedly induced. In vitro kinase ...
Prognostic Role of the Cyclin-dependent Kinase Inhibitor p27 in Non-Small Cell Lung Cancer. Vincenzo Esposito, Alfonso Baldi, ... Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor ... Prognostic Role of the Cyclin-dependent Kinase Inhibitor p27 in Non-Small Cell Lung Cancer ... Prognostic Role of the Cyclin-dependent Kinase Inhibitor p27 in Non-Small Cell Lung Cancer ...
These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase ... p27 is a potent inhibitor of Cdks. In quiescent cells p27 accumulates without an increase in mRNA or protein synthesis. Cell ... This finding raises the question of whether and how phosphorylation by these kinases is involved in the process of p27 ... The specific proteolysis of p27 is probably involved in the pathway of activation of Cdks. p27 is a phosphoprotein and its ...
cyclin-dependent protein kinase activity; cyclin-dependent protein kinase activity; cyclin-dependent protein kinase inhibitor ... CDKN1B; cyclin-dependent kinase inhibitor 1B (p27, Kip1); cyclin-dependent kinase inhibitor 1B; KIP1; P27KIP1; MEN4; CDKN4; ... also known as cyclin-dependent kinase inhibitor 1B, belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor ... Recombinant Human Cyclin-Dependent Kinase Inhibitor 1B (p27, Kip1), His-tagged. Download Datasheet See All CDKN1B Products. ...
The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found to ... N2 - The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found ... AB - The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found ... abstract = "The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 ...
... p27, Kip1) Gene from ProteoGenix cat# PTXBC001971. Shop among our wide range of DNA & cDNAavailable at highly competitive ... Buy online CDKN1B-cyclin-dependent kinase inhibitor 1B ( ... cyclin-dependent kinase inhibitor 1B; cyclin-dependent kinase ... cyclin-dependent kinase inhibitor 1B (p27, Kip1). Synonyms: CDKN4; KIP1; MEN1B; MEN4; P27KIP1; ... More info about CDKN1B-cyclin-dependent kinase inhibitor 1B (p27, Kip1) Gene. Proteogenix catalog: PTXBC001971. ...
The cyclin-dependent kinase inhibitor p27Kip1 has been shown to influence cell number in several developing tissues, by ... In normal mice, p27 Kip1 is evident in a subset of receptor and presynaptic taste cells beginning about 3 days post-injection, ... cell types and general structure contrasts with the hyperplasia and tissue disruption seen in certain developing p27 Kip1 -null ... investigated its involvement in the control of taste cell replacement by examining adult mice with targeted ablation of the p27 ...
... a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). The progression of cells through the cell ... cyclin-dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995, 11: 211 ... The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the ... Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. Two major classes of CDK ...
p27 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2. In mouse fibroblasts, p27 ... we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. ... Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, ... Cyclin-Dependent Kinase 2 * Cyclin-Dependent Kinase 4 * Cyclin-Dependent Kinase Inhibitor p27 ...
Cyclin-Dependent Kinase Inhibitor p27. Cyclins / drug effects. Cysteine Endopeptidases. Cysteine Proteinase Inhibitors / ... 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 616-91-1/Acetylcysteine; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine ... 16236519 - Mammalian cyclin-dependent kinases.. 8797939 - The nature and significance of liver cell vacuolation following ... Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and ...
p27Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent VSMCs and inhibits the G1 to S phase transition ... Under normal conditions, vascular injury promotes degradation of p27Kip1 protein in an mTOR dependent manner. Recent reports ... from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may ... inhibitors. Inhibition of mTOR blocks protein synthesis, cell cycle progression, and cell migration. Key to the effects on cell ...
Cyclin-dependent kinase inhibitor 1B. C. 72. Homo sapiens. Mutation(s): 0 Gene Names: CDKN1B, KIP1. ... p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition.. Guiley, K.Z., Stevenson, J.W., ... Cyclin-dependent kinase 4. B. 302. Homo sapiens. Mutation(s): 2 Gene Names: CDK4. EC: 2.7.11.22. ... We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1 ...
p27. is a cyclin-dependent kinase (cdk) inhibitor. It inhibits cell cycle progression in G1 phase by preventing activation of ... Cyclin-dependent kinase inhibitor p27 and Polycomb-group protein EZH2 are both promising immunohistochemical markers for ... cyclin E-cdk2 and cyclin D/-cdk4 complexes [67]. Loss of p27 has been widely associated with progression of different tumor ... p27 expression in prostate cancer needle-biopsies correlates well with the p27 labeling in radical prostatectomy samples [64, ...
Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC ...
... p21 and p27. Together they form a unique fingerprint. * Cyclin-Dependent Kinase Inhibitor p27 Medicine & Life Sciences ... T2 - Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27 ... Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27. Nephrology Dialysis Transplantation, 18(SUPPL. 3), iii9 ... Vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27, Nephrology Dialysis Transplantation, vol. 18, no. ...
Cyclin-Dependent Kinase Inhibitor p27 - Similar structures search, synonyms, formulas, resource links, and other chemical ... Substance Name: Cyclin-Dependent Kinase Inhibitor p27. RN: 147604-94-2. Note. *. A cyclin-dependent kinase inhibitor that ... It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it ... coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. ...
Cyclins, cyclin-dependent kinases (CDKs) and the CDK inhibitor p27(kip1) are known to be involved in the regulation of G(1)/S ... Cell type-specific induction of cyclin D and cyclin-dependent kinase inhibitor p27(kip1) expression by estrogen in rat ... Here we studied the cell-specific regulation of D-type cyclin (D(1-3)), of cyclin A and E, of CDK(2) and p27(kip1) by 17beta- ... The differential regulation of cyclins and p27(kip1) in the epithelium and stroma of the endometrium appear indicative of ...
Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in ... has been reported to have a homozygous germline p27 (CDKN1B) mutation. Recently, two MEN1 mutation-negative MEN1 syndrome ... Cyclin-Dependent Kinase Inhibitor p27. Grant support. *G0701307/Medical Research Council/United Kingdom ...
PCAF REGULATES THE STABILITY OF THE TRANSCRIPTIONAL REGULATOR AND CYCLIN-DEPENDENT KINASE INHIBITOR P27 KIP1.. You are here. ... Home » Publications » PCAF REGULATES THE STABILITY OF THE TRANSCRIPTIONAL REGULATOR AND CYCLIN-DEPENDENT KINASE INHIBITOR P27 ... PCAF REGULATES THE STABILITY OF THE TRANSCRIPTIONAL REGULATOR AND CYCLIN-DEPENDENT KINASE INHIBITOR P27 KIP1. ...
Cyclin-Dependent Kinase Inhibitor p27. Grant support. *12183/Cancer Research UK/United Kingdom ... with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors ...
Buy our Recombinant Human p27 KIP 1 protein. Ab56279 is a full length protein produced in Escherichia coli and has been ... Cyclin dependent kinase inhibitor p27. *Cyclin-dependent kinase inhibitor 1B. *Cyclin-dependent kinase inhibitor 1B (p27, Kip1) ... Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in ... Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or ...
Repression of transcription of the p27Kip1 cyclin-dependent kinase inhibitor gene by c-Myc *William Yang ... Rights & permissionsfor article Repression of transcription of the ,i,p27,/i,,sup,Kip1,/sup, cyclin-dependent kinase inhibitor ... Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions *Robert W Maul ... Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice *Peter Langfelder ...
siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B). US7615541. Nov 3, 2006. Nov 10, 2009. Dharmacon, Inc ... siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B). US20080227967 *. Jun 13, 2007. Sep 18, 2008. ... SiRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B). US8022198. Aug 10, 2009. Sep 20, 2011. Dharmacon, ... siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B). US8232386. Oct 27, 2011. Jul 31, 2012. Dharmacon, ...
... cyclin-dependent kinase inhibitor 1; p27, cyclin-dependent kinase inhibitor 1b; PIT, phase inversion temperature; PLGA, poly( ... EGF-dependent PI3K pathway, TGF-β), cell cycle arrest (cyclin D1, p21, p27), anti-angiogenesis (VEGF, VEGFR-2) and anti- ... EGF-dependent PI3K, epidermal growth factor-dependent phosphatidylinositol-3-kinases; EMT, epithelial-mesenchymal transition; ... 2018). Identification of inhibitors synergizing gemcitabine sensitivity in the squamous subtype of pancreatic ductal ...
Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in ... Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. Involved in ... Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or ... Cyclin-dependent kinase inhibitor 1B. Alternative name(s):. Cyclin-dependent kinase inhibitor p27 ...
Rabbit polyclonal p27 KIP 1 (phospho T198) antibody validated for WB, ELISA and tested in Human and Mouse. Referenced in 1 ... Cyclin dependent kinase inhibitor p27 antibody. *Cyclin-dependent kinase inhibitor 1B (p27, Kip1) antibody ... Cyclin-dependent kinase inhibitor p27 antibody. *Cyclin-dependent kinase inhibitor p27 Kip1 antibody ... Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in ...
SNHG5, small nucleolar RNA host gene 5; CDK2, cyclin-dependent kinase 2; p27, cyclin-dependent kinase inhibitor 1B; si, small ... SNHG5, small nucleolar RNA host gene 5; si small interfering; p27, cyclin-dependent kinase inhibitor 1B; BC, bladder carcinoma. ... western blot assay demonstrated that the level of cyclin-dependent kinase 2 (CDK2) was decreased while the level of p27 was ... The oncogenic function of SNHG5 is in a p27-dependent manner. To determine whether p27 was involved in the si-SNHG5-mediated ...
Mouse Monoclonal Anti-p27/Kip1 Antibody (SX53G8) [DyLight 405LS]. Validated: WB, ELISA, Flow, ICC/IF, IHC-Fr, IHC-P, IP. Tested ... cyclin-dependent kinase inhibitor 1B (p27, Kip1). *cyclin-dependent kinase inhibitor 1B ... Home » p27/Kip1 » p27/Kip1 Antibodies » p27/Kip1 Antibody (SX53G8) [DyLight 405LS] ... p27/Kip1 Antibody (SX53G8) [DyLight 405LS] Summary. Immunogen. Purified GST-p27 fusion protein of human origin ...
  • p27 is identical to p27Kip1, a cyclin-Cdk inhibitor present in TGF beta-treated cells. (nih.gov)
  • This MAb recognizes a 27kDa protein, identified as the p27Kip1, a cell cycle regulatory mitotic inhibitor. (novusbio.com)
  • Recognizes a 27kDa protein, identified as the p27Kip1, a cell cycle regulatory mitotic inhibitor. (novusbio.com)
  • We show here that loss of the cyclin-dependent kinase inhibitor p27Kip1 has very specific effects on a population of CNS progenitors responsible for adult neurogenesis. (jneurosci.org)
  • 1997 ) Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. (biologists.org)
  • The cyclin-dependent kinase (Cdk) inhibitor p27Kip1 may be involved in regulating re-entry of residual hepatocytes into the cell cycle upon loss of liver tissue by partial hepatectomy (PH). (frontiersin.org)
  • As in other proliferation-competent epithelial cells, the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 (Kip1) is expressed in the nuclei of quiescent hepatocytes ( Nakayama and Nakayama, 1998 ). (frontiersin.org)
  • CDKN1B, also known as cyclin-dependent kinase inhibitor 1B, belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. (creativebiomart.net)
  • A rat strain with multiple endocrine tumours, a phenotypic overlap of both MEN1 and MEN2, has been reported to have a homozygous germline p27 (CDKN1B) mutation. (cdc.gov)
  • Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. (nih.gov)
  • The CDKN1B gene provides instructions for making a protein called p27. (nih.gov)
  • Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. (nih.gov)
  • CDKN1B (Cyclin Dependent Kinase Inhibitor 1B) is a Protein Coding gene. (genecards.org)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • These mice express a cyclin-dependent kinase inhibitor 1B ( Cdkn1b ) cDNA under the direction of the tetracycline operator. (jax.org)
  • CDKN1B, or p27, is a cell cycle inhibitor protein which acts by arresting cell division at G1. (jax.org)
  • The TREP27 transgene was designed with the tetracycline operator ( tetO or tet-operator) driving expression of cyclin-dependent kinase inhibitor 1B ( Cdkn1b ) cDNA. (jax.org)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
  • Cyclins, cyclin-dependent kinases (CDKs) and the CDK inhibitor p27(kip1) are known to be involved in the regulation of G(1)/S phase transition by estrogen in the rodent endometrium. (scienceexchange.com)
  • The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
  • In mammalian cells, cell cycle traversal is regulated by cyclins and cyclin-dependent kinases (CDKs) that are in turn controlled by CDK inhibitors (CKIs) ( 31 ). (asm.org)
  • Cell division relies on the activation of cyclins, which bind to CDKs to induce cell cycle progression towards S phase and later to initiate mitosis. (thermofisher.com)
  • Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
  • Cancer is a disease of uncontrolled proliferation, and since CDKs are a central component of the cell cycle engine, great effort has been expended in developing CDK inhibitors as anticancer agents. (aspetjournals.org)
  • and is modulated by the enzymatic activity of cyclin-dependent kinases (CDKs). (jneurosci.org)
  • See also CDK inhibitor for inhibitors of various CDKs. (wikipedia.org)
  • The coordinated expression of cyclins, cdks, and cdk inhibitors is often deregulated in cancer (2) . (aacrjournals.org)
  • p27 kip1 acts primarily by complexing with cyclins D1 and E, thereby inhibiting the function of these cdks. (aacrjournals.org)
  • Cyclin dependent kinases (CDKs) are typical serine/threonine kinases that display the 11 subdomains shared by all kinases. (sigmaaldrich.com)
  • Following IL-6 treatment of LNCaP, Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while accumulation of CDK inhibitor p27(Kip1) was rapidly and markedly induced. (nih.gov)
  • Further, a significant amount of p27(Kip1) was co-precipitated with CDK2, CDK4 and CDK6, as detected in immunoprecipitation experiments. (nih.gov)
  • This protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (creativebiomart.net)
  • p27 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2. (nih.gov)
  • Recombinant p27 is a potent inhibitor of cyclin D1-Cdk4 and cyclin A-Cdk2 protein kinase activity and a weaker inhibitor of cyclin B1-Cdc2. (nih.gov)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Upregulation of cyclin D2 and D3 in activated B-CLL cells was inhibited while the expression of cdk2, cdk4, and cyclin E remained unchanged. (biomedsearch.com)
  • Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. (uniprot.org)
  • Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (uniprot.org)
  • These cyclin-CDK complexes, as well as cyclin E-CDK2 complexes later in the cell cycle, phosphorylate retinoblastoma protein (Rb). (asm.org)
  • This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. (biomedsearch.com)
  • 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. (asm.org)
  • Phosphorylation of pRb during G 1 phase is carried out by cyclin D-Cdk4 and cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes ( 44 , 50 , 55 ). (asm.org)
  • In contrast, we have shown previously that although serum-stimulated senescent HDF (IMR90) have abundant cyclin E-Cdk2 complexes, they lack cyclin E-associated kinase activity, a finding consistent with their failure to phosphorylate pRb ( 14 ). (asm.org)
  • Regulation of Cdk2 activity by activating (Thr-160) and inhibiting phosphorylations (Thr-14, Tyr-15) did not account for the lack of cyclin E-Cdk2 kinase activity in senescent cells, i.e., even though approximately one-half of the cyclin E-associated Cdk2 was phosphorylated on Thr-160, treatment with Cdc25 phosphatase to dephosphorylate Thr-14 and Tyr-15 did not increase activity. (asm.org)
  • The finding that senescent HDF contain elevated amounts of the ubiquitously acting cyclin-dependent kinase inhibitor (CKI) p21 Sdi1,Cip1,Waf1 (p21) ( 40 ) suggested instead that cyclin E-Cdk2 complexes in senescent cells might be inactivated by increased binding of p21. (asm.org)
  • We hypothesized that a variation in the inactivation of cdk2 and cdk4 during the G 1 phase of the cell cycle by p27 Kip1 , p21 Cip1 , and p16 Ink4 leads to different effects on VSMC growth in vitro and in vivo. (ahajournals.org)
  • Methods and Results -The expression of p27 Kip1 and p21 Cip1 in serum-stimulated VSMCs inactivated cdk2 and cdk4, leading to G 1 growth arrest. (ahajournals.org)
  • p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
  • Progression through G 1 and entry into the S phase is regulated by the formation and activation of cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D-cdk4/6 and cyclin E-cdk2. (ahajournals.org)
  • We hypothesized that differences in the activation of cdk2 and cdk4 by p27 Kip1 , p21 Cip1 , and p16 Ink4 would lead to differential effects on VSMC growth. (ahajournals.org)
  • To test this hypothesis, we examined the effects of p27 Kip1 , p21 Cip1 , and p16 Ink4 on cdk2 and cdk4 activity, G 1 growth arrest, and VSMC proliferation in vitro and in vivo. (ahajournals.org)
  • A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity. (abcam.com)
  • More recent work indicates that the induction of cyclin D-CDK complexes results in the redistribution of CDK inhibitor p27 Kip1 from cyclin E-CDK2 complexes to cyclin D-CDK4/6 complexes, thereby triggering the kinase activity of cyclin E-CDK2 holoenzyme ( 6 ). (pnas.org)
  • These creative ways to develop CDK inhibitors are presented along with crystal structures of these agents complexed with CDK2 to highlight differences in their binding sites and mechanisms of action. (aspetjournals.org)
  • CDK2, in contrast, is positively regulated by cyclin E and negatively regulated by the Kips. (jneurosci.org)
  • Rb reduces its binding to E2F and thereby allows E2F-mediated activation of the transcription of cyclin E and cyclin A, which bind to Cdk1 and Cdk2 respectively to create complexes that continue with Rb phosphorylation. (wikipedia.org)
  • p21 Cip1 (alternatively p21 Waf1 ), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 , is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, [5] though is primarily associated with inhibition of CDK2 . (wikipedia.org)
  • The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin - CDK2 , - CDK1 , and - CDK4 /6 complexes, and thus functions as a regulator of cell cycle progression at G 1 and S phase . (wikipedia.org)
  • also found that γ-irradiation of fibroblasts induced a p53 and p21 dependent cell cycle arrest, here p21 was found bound to inactive cyclin E / CDK2 complexes. (wikipedia.org)
  • We have shown that duplication of the centrosome, the microtubule organizing center of animal cells, is dependent on the cell cycle kinase cdk2, and on cell cycle-specific proteolysis. (stanford.edu)
  • The Cdk2-cyclin-E complex is responsible for phosphorylation of p27 at Thr-187, 5 6 whereas Akt has been shown to phosphorylate p27 directly on Ser-10, Thr-157, and Thr-198. (arvojournals.org)
  • The CKIs of the Cip/Kip family are more broadly reactive and include p21 Cip1 , p27 Kip1 , and p57 Kip2 ( 32 ). (asm.org)
  • Cdk4 activity is also significantly decreased in the treated cells and is accompanied by an increased expression of the Cdk inhibitor p21(CIP1). (biomedsearch.com)
  • Blockage of K + channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27 Kip1 and p21 CIP1 in OP cells. (jneurosci.org)
  • Our results demonstrate that blockage of K + channels and cell depolarization induce G1 arrest in the OP cell cycle through a mechanism that may involve p27 Kip1 and p21 CIP1 and further support the conclusion that OP cell cycle arrest and differentiation are two uncoupled events. (jneurosci.org)
  • The Kip/Cip CKIs, p27 Kip1 and p21 Cip1 , are upregulated during arterial repair and negatively regulate the growth of vascular smooth muscle cells (VSMCs). (ahajournals.org)
  • Conclusions -p27 Kip1 and p21 Cip1 are potent inhibitors of VSMC growth compared with p16 Ink4 because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G 1 phase of the cell cycle. (ahajournals.org)
  • The CKIs p27 Kip1 and p21 Cip1 inactivate the cyclin-CDK complexes in the G 1 phase leading to cell cycle arrest, and thus function in growth regulation and wound repair. (ahajournals.org)
  • 6 The molecular mechanisms accounting for the differences in the expression and function of p27 Kip1 , p21 Cip1 , and p16 Ink4 in blood vessels are not known. (ahajournals.org)
  • Recombinant replication-defective adenoviral vectors encoding human p27 Kip1 , p21 Cip1 , p16 Ink4 , and a control vector, AdΔE1, were constructed in an E1A/E3-deleted adenoviral plasmid containing a cytomegalovirus promoter and bovine growth human polyadenylation signal. (ahajournals.org)
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
  • In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27 Kip1 and p21 Cip1 . (pnas.org)
  • Invitrogen is now offering two new assay kits to measure p27 Kip1 and p21 Waf1/Cip1 protein levels in cell lysates. (thermofisher.com)
  • CDK function is tightly regulated by cell cycle inhibitors such as p21 Waf1/Cip1 and p27 Kip1 proteins. (thermofisher.com)
  • Following anti-mitogenic signals or DNA damage, p21 Waf1/Cip1 and p27 Kip1 bind to cyclin-CDK complexes to inhibit their catalytic activity and induce cell cycle arrest. (thermofisher.com)
  • Stable ERRγ expression by retroviral transduction suppressed significantly both in vitro cell growth and in vivo tumorigenicity of two prostate cancer cell lines, LNCaP and DU145, as evidenced by a cell-cycle arrest at G 1 -S transition and also induction of two cyclin-dependent kinase inhibitors p21 WAF1/CIP1 and p27 KIP1 . (aacrjournals.org)
  • Liver mRNA levels of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF)-β, cyclin-dependent kinase inhibitor p27 kip (p27), and cyclin-dependent kinase inhibitor p21 WAF1/CIP1 (p21) were quantified by real-time polymerase chain reaction. (aspetjournals.org)
  • Based on their protein sequence homologies and putative cdk targets, cdk inhibitors belong to one of two families: the CIP/KIP family (p21 Waf1/Cip1 , p27 kip1 , and p57 kip2 ), which inhibits a broad range of cyclin/cdk complexes and the INK4 family (p15 Ink4b , p16 Ink4a , p18 Ink4c , and p19 Ink4d ), which inhibit mainly cdk4 and cdk6. (aacrjournals.org)
  • In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. (garvan.org.au)
  • These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. (garvan.org.au)
  • Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. (garvan.org.au)
  • The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) downstream of cortactin were confirmed by the transient knockdown of each CDKI by specific small interfering RNAs, which led to partial rescue of cell cycle progression. (garvan.org.au)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. (uniprot.org)
  • Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. (uniprot.org)
  • CKIs act as brakes for the cell cycle, restraining the activity of cyclin-CDK complexes to maintain cells in the quiescent G 0 /G 1 phase or to induce cell cycle exit in proliferating cells. (asm.org)
  • The irreversible G 1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G 1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). (asm.org)
  • 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. (asm.org)
  • Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by ≤50% compared to young cells. (asm.org)
  • The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. (genecards.org)
  • Inhibitors of the kinase inhibitory protein (Kip) family can also bind CDK4/cyclin D complexes, although with lower affinity than the INKs, but this event does not result in efficient functional inhibition of enzymatic activity ( Sherr and Roberts, 1995 ). (jneurosci.org)
  • In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. (wikipedia.org)
  • Cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. (wikipedia.org)
  • Cyclin A and E dependent kinase complexes also function to inhibit the E3 ubiquitin ligase APC/C activating subunit Cdh1 through phosphorylation, which stabilizes substrates such as cyclin A. The coordinated activation of this sequence of interrelated positive feedback loops through cyclins and cyclin dependent kinases drives commitment to cell division to and past the G1/S checkpoint. (wikipedia.org)
  • [12] [13] The binding of p21 to CDK complexes occurs through p21's N-terminal domain, which is homologous to the other CIP/KIP CDK inhibitors p27 and p57 . (wikipedia.org)
  • [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
  • Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
  • Kip1 down-regulation occurs precisely within the intervall between surgery and onset of DNA synthesis which supports the hypothesis that it mediates activation of G0/0S-phase Cdk/cyclin-complexes and re-entry of hepatocytes into the cell cycle. (frontiersin.org)
  • Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found mutated in human tumors. (aacrjournals.org)
  • 2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
  • p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors. (uniprot.org)
  • This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (genecards.org)
  • We further showed by reporter assay that induction of p21 and p27 by ERRγ was mediated through direct transactivation of their gene promoters. (aacrjournals.org)
  • In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. (biologists.org)
  • Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
  • 6 ⇓ - 8 In 1994, 2 independent groups cloned the genes involved in this translocation and illustrated the fusion of the nucleophosmin ( NPM ) gene on chromosome 5q35 to the previously unidentified gene anaplastic lymphoma kinase ( ALK ) gene on 2p23. (bloodjournal.org)
  • Recent studies defining point mutations in the bcr-abl oncogene or c-kit receptor tyrosine kinase encoding gene, which underlie acquired resistance to imatinib (STI571/Gleevec) in chronic myelogenous leukemia or gastrointestinal stromal tumors ( 1 ), have, if anything, reinforced the perceived importance of mutation-driven mechanisms responsible for drug resistance. (aacrjournals.org)
  • 3 Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain. (jci.org)
  • Kallikrein gene transfer into cultured rat VSMCs resulted in time-dependent secretion of recombinant human tissue kallikrein and inhibition of cell proliferation. (ahajournals.org)
  • Furthermore, p27(Kip1) controls Bez235 sensitivity in a gene dose-dependent fashion in murine PDAC cells and lowering of p27(Kip1) decreases Bez235 responsiveness in murine PDAC models. (jove.com)
  • It's also possible that C/EBPα and/or C/EBPε transcription factors control the gene expression … More of these CDK inhibitors. (nii.ac.jp)
  • G-CSF dependent expression of ERO1-L gene appeared to be in control of Stat3 activation during neutrophil differentiation. (nii.ac.jp)
  • Using a yeast interaction screen to search for proteins that interact with cyclin D1-Cdk4, we identified a 27 kDa mouse protein related to the p21 cyclin-Cdk inhibitor. (nih.gov)
  • The INK4 proteins include p16 INK4a , p15 INK4b , p18 INK4c , and p19 INK4d , which are specific inhibitors of CDK4 and CDK6 ( 3 ). (asm.org)
  • Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. (wikipedia.org)
  • Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (nih.gov)
  • Some mutations impair the protein's ability to interact with regulatory proteins, while others lead to the production of an unstable version of p27 that is quickly broken down. (nih.gov)
  • These proteins are believed to drive cell cycle progression by associating with their kinase partners, cyclin-dependent kinases, and by directing phosphorylation of critical cellular substrates. (pnas.org)
  • As cyclin-dependent kinase (CDK) inhibitors, both proteins are negative cell cycle regulators that play an important role in tumor suppression. (thermofisher.com)
  • Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. (wikipedia.org)
  • In mice and humans, two more cyclin D proteins have been identified. (wikipedia.org)
  • These findings suggest that the pro-drug form of another β-lactone, lovastatin, similar in structure to lactacystin, may inhibit the ubiquitin-mediated proteolysis of key regulatory proteins such as the cyclins and CKIs. (pnas.org)
  • Bortezomib is a potent and selective inhibitor of the 26S proteasome, 8 , 9 a multisubunit protein complex present in the nucleus and the cytoplasm of all eukaryotic cells 10 that is responsible for the degradation of ubiquitinated proteins. (bloodjournal.org)
  • These proteins are one of the only endogenous inhibitors of the growth of cells and since uncontrolled cell proliferation is the hallmark of cancer, our laboratory has been intrigued by and dedicated to understanding the role for TGF-βs in neoplastic development and cancer progression. (springer.com)
  • Cells expressing MLL fusion proteins turned out to be sensitive to inhibitors of GSK3. (medpagetoday.com)
  • Retinoic acid-induced changes in cell cycle-related proteins occurred in 4-6 h, including reduced cyclin E expression in bromodeoxyuridine (BrdU)-labeled cells, before the onset of cell differentiation as indicated by an increase in the percentage of G1 phase cells and a reduction in S phase cells at 24 h. (ovid.com)
  • We investigated p27 protein expression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transformation and/or progression. (aacrjournals.org)
  • These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase (Cdk) activity. (semanticscholar.org)
  • p27 has the hallmarks of a negative regulator of G1 progression and may mediate TGF beta-induced G1 arrest. (nih.gov)
  • RESULTS: Lactacystin blocked cell cycle progression in activated B-CLL cells and inhibited degradation of p27. (biomedsearch.com)
  • Key to the effects on cell cycle progression and cell migration is the inhibition of mTOR-mediated degradation of p27 Kip1 protein. (mdpi.com)
  • It has been hypothesized that voltage-dependent K + channel activity could regulate mitogenesis in the nervous system by maintaining the membrane potential hyperpolarized, a condition necessary for progression through G1 phase restriction points ( Wonderlin and Strobl, 1996 ). (jneurosci.org)
  • and (2) cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected by ion channel activity or changes in membrane potential. (jneurosci.org)
  • Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. (wikipedia.org)
  • By blocking cell cycle progression, p27 prevents cells from dividing too quickly or at the wrong time. (nih.gov)
  • For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. (nih.gov)
  • The progression of mammalian cells through the G 1 phase of the cell cycle is governed by two classes of cyclins, namely D-cyclins and cyclin E. The D-cyclins (cyclins D1, D2, and D3) are expressed in an overlapping, redundant fashion in all proliferating cell types. (pnas.org)
  • D-cyclins are thought to drive cell cycle progression by associating with their catalytic partners (termed cyclin-dependent kinases CDK4 and CDK6) and by guiding these kinases to their cellular substrates ( 1 ). (pnas.org)
  • Thus, D-cyclins also control cell cycle progression in a kinase-independent manner, via their interaction with p27 Kip1 . (pnas.org)
  • Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. (biologists.org)
  • Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. (wikipedia.org)
  • In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. (wikipedia.org)
  • Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression. (wikipedia.org)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
  • p27 Kip1 (p27) is an important regulator of G 1 progression. (arvojournals.org)
  • 1 However, in the mitogenic pathway, p27 is degraded through the ubiquitin-proteasome machinery, leading cell cycle progression from the G 1 to the S phase. (arvojournals.org)
  • The cyclin-dependent kinase inhibitor p27 kip1 regulates cellular progression from G 1 to S phase. (aacrjournals.org)
  • Several studies have shown that loss of p27 kip1 protein expression is associated with disease progression in various malignancies. (aacrjournals.org)
  • Cellular progression through the cell cycle is governed by cyclin-dependent kinase (cdk) that is regulated by phosphorylation, activated by binding of cyclins, and inhibited by cdk inhibitors. (aacrjournals.org)
  • Overall, RA increased the functionality of pRb as an inhibitor of cell cycle progression. (ovid.com)
  • appeared to prevent the cell-cycle progression from G1 to S during G-CSF dependent neutrophil differentiation. (nii.ac.jp)
  • 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. (curehunter.com)
  • p27 Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent VSMCs and inhibits the G 1 to S phase transition and cell migration. (mdpi.com)
  • Moreover, the overexpression of p21 and p27 inhibits cell proliferation. (elsevier.com)
  • Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. (biomedsearch.com)
  • A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). (wikipedia.org)
  • Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. (wikipedia.org)
  • Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D. Cyclin D possesses a tertiary structure similar to other cyclins called the cyclin fold. (wikipedia.org)
  • Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and caspase-dependent and -independent pathways. (biomedsearch.com)
  • CONCLUSION: Proteasome inhibition is highly effective in proliferating B-CLL cells and induces apoptosis using a caspase-dependent and -independent pathway. (biomedsearch.com)
  • Recent reports from our lab suggest that in the presence of diabetes mellitus, elevation of extracellular signal response kinase activity may promote decreased p27 Kip1 mRNA and produce a relative resistance to mTOR inhibition. (mdpi.com)
  • Moreover, we also showed that a selective ERRγ-agonist, DY131, could potentiate the ERRγ-induced growth inhibition in LNCaP-ERRγ and DU145-ERRγ cells in a dose-dependent manner compared with respective parental cells. (aacrjournals.org)
  • In addition, many of the properties of proteasome inhibition by the pro-drug are the same as the specific proteasome inhibitor lactacystin. (pnas.org)
  • Here we demonstrate that 5 different MM cell lines display similar patterns of sensitivity to 3 proteasome inhibitors (PIs) but respond differently to specific NF-κB inhibition. (bloodjournal.org)
  • Therefore, we have uncovered a context-dependent phenotype of TSC mutants in adult ISCs, such that the excessive growth leads to inhibition of division. (rupress.org)
  • Rapamycin influences the cell cycle by up-regulation of p27, down-regulation of p21, and inhibition of p70 s6k phosphorylation. (aspetjournals.org)
  • 5 Specific Ang II receptor antagonists can also partially inhibit neointima formation, which suggests that the inhibition of neointima formation by ACE inhibitors is, in part, because of a decreased level of Ang II. (ahajournals.org)
  • The increase in local kinin accumulation may also be involved in the inhibition of neointima formation because icatibant, a bradykinin B 2 receptor antagonist, can partially block the protective effect of ACE inhibitors. (ahajournals.org)
  • Dr. Cleary and colleagues said the research "provides a rationale to develop inhibitors with suitable pharmacodynamic properties for clinical trials to determine whether GSK3 inhibition may have therapeutic efficacy in a distinctive subset of poor prognosis leukemia. (medpagetoday.com)
  • Inhibition of GSK3 apparently causes cell-cycle arrest, the researchers said, probably through the action of p27 Kip1 . (medpagetoday.com)
  • Proliferation defect of Pfn1 overexpressers can be partly rescued by silencing p27 expression thus suggesting a critical role of p27 in Pfn1-induced growth inhibition of MDA-MB-231 cells. (pubmedcentralcanada.ca)
  • Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. (nih.gov)
  • The phenotypes of these mice suggest that loss of p27 causes an alteration in cell proliferation that can lead to specific endocrine dysfunction. (nih.gov)
  • In order to elucidate the mechanism of parathyroid cell proliferation, the expression of CDKIs, p21 and p27, and the VDR was analysed immunohistochemically, and compared among nodular and diffuse hyperplastic parathyroid glands, and histologically normal parathyroid glands. (elsevier.com)
  • p16 Ink4 was a weak inhibitor of intimal VSMC proliferation in injured arteries ( P =NS), and it did not significantly reduce intima/media area ratios ( P =NS), which is consistent with its minor effects on VSMC growth in vitro. (ahajournals.org)
  • p27 Kip1 is constitutively expressed in normal arteries, is downregulated after arterial injury, becomes upregulated during the later phases of arterial repair, and is inversely correlated with VSMC proliferation. (ahajournals.org)
  • Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (thefreedictionary.com)
  • In the present work we set out to examine the significance of cyclin D1-p27 Kip1 interaction in driving cell proliferation within the context of a living animal. (pnas.org)
  • We reasoned that analyses of these cyclin D1 −/− p27 −/− animals would provide a stringent test for the significance of cyclin D1-p27 Kip1 interaction in controlling the cell proliferation of various cyclin D1-dependent lineages. (pnas.org)
  • Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear. (biologists.org)
  • This hypothesis is strengthened by our recent findings that 2-ME is a potent inhibitor of SMC proliferation and migration and extracellular matrix production 1 and that sequential metabolism of estradiol to methoxyestradiols, such as 2-ME, plays a major role in mediating the inhibitory effects of estradiol on SMC growth. (ahajournals.org)
  • Vary the extraction solvent component extracted will also differ, first with the MTT assay primary efficacy preferred extraction methods on hepatoma cells (Hep 3B), the results from the analysis showed that MTT, VA to inhibit the proliferation of Hep 3B, in a time and dose-dependent manner. (ncl.edu.tw)
  • GSK3 supports MLL leukemia cell proliferation and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27 Kip1 . (medpagetoday.com)
  • In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were significantly inhibited in IL-6-treated LNCaP. (nih.gov)
  • Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
  • Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin-proteasome pathway. (elsevier.com)
  • In the following experiments, we found that CDCA2 regulated CCND1 expression through activating the PI3K/AKT pathway, and confirmed this using a specific PI3K inhibitor (LY294002). (springer.com)
  • The abundance of cyclins is generally regulated by protein synthesis and degradation through an APC/C dependent pathway. (wikipedia.org)
  • The ubiquitin pathway also regulates the levels of cyclin-dependent kinase inhibitors (CKIs) p27 and p21 ( 5 - 7 ). (pnas.org)
  • Additionally, the lovastatin-mediated G 1 arrest and p21/p27 induction occur independently of the ras signaling pathway/function ( 22 , 23 ). (pnas.org)
  • TCR activation decreases the steady state protein levels of FLIP (FLICE-like inhibitory protein), an inhibitor of the Fas signaling pathway. (jimmunol.org)
  • In this study we have investigated whether the sensitization of T cells to Fas-mediated apoptosis following TCR stimulation is mediated by the down-regulation of inhibitors of the Fas signaling pathway such as FLIP. (jimmunol.org)
  • Does auxin act through multiple pathways to these diverse ends, or is there a single pathway that is dependent on the spatial, temporal, and environmental context in which auxin is received? (plantcell.org)
  • Several evidences point to the phosphatidylinositol 3-kinase (PI3K)-mTOR pathway as a promising signaling node for targeted therapeutic intervention. (jove.com)
  • Dr. Cleary added that it might be possible to target elements further downstream in the GSK3 pathway such as p27. (medpagetoday.com)
  • In this report we show that this stabilization of p21 and p27 may be the result of a previously unknown function of the pro-drug, β-lactone ring form of lovastatin to inhibit the proteasome degradation of these CKIs. (pnas.org)
  • Inhibitors were used to inhibit proteasomal degradation and nuclear export of the phosphorylated p27. (arvojournals.org)
  • Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. (nih.gov)
  • Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate t. (nih.gov)
  • Thus, IL-6-induced G1 arrest appears to be due to the accumulation of p27(Kip1). (nih.gov)
  • PKC-dependent phosphorylation of p27 at T198 contributes to p27 stabilization and cell cycle arrest. (semanticscholar.org)
  • Overexpression of p27 in Saos-2 cells causes G1 arrest. (nih.gov)
  • are not involved in ion channel-dependent cell cycle arrest in OP cells. (jneurosci.org)
  • 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. (asm.org)
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
  • In addition, knockdown of INPP5E counteracted the growth arrest caused by an miR‑598‑inhibitor. (spandidos-publications.com)
  • In this paper we present the finding that lovastatin arrests cells by inhibiting the proteasome, which results in the accumulation of p21 and p27, leading to G 1 arrest. (pnas.org)
  • Previously, we reported that lovastatin can be used to arrest cultured cells in the G 1 phase of the cell cycle, resulting in the stabilization of the cyclin-dependent kinase inhibitors (CKIs) p21 and p27. (pnas.org)
  • How lovastatin induces G 1 arrest and simultaneously increases p21 and/or p27 currently is undefined. (pnas.org)
  • Studies of p53 dependent cell cycle arrest in response to DNA damage identified p21 as the primary mediator of downstream cell cycle arrest. (wikipedia.org)
  • Lactacystin is a specific inhibitor of the proteasome and is a potent apoptosis inductor in resting peripheral B-CLL cells. (biomedsearch.com)
  • p21 is a potent cyclin-dependent kinase inhibitor (CKI). (wikipedia.org)
  • The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. (elsevier.com)
  • One class of agents that are highly effective in the prevention of in-stent restenosis is the mammalian Target of Rapamycin (mTOR) inhibitors. (mdpi.com)
  • Inhibitors of the mammalian Target of Rapamycin (mTOR) are highly effective at blocking intimal hyperplasia and have been used in drug-eluting stents. (mdpi.com)
  • D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. (pnas.org)
  • All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. (nih.gov)
  • Kinases regulate many essential cellular processes. (thefreedictionary.com)
  • Antigen receptor signaling or exposure to growth factors triggers de novo synthesis of D-type cyclins, which then associate with their catalytic partners CDK4 or CDK6. (asm.org)
  • Under normal conditions, vascular injury promotes degradation of p27 Kip1 protein in an mTOR dependent manner. (mdpi.com)
  • 11 The differential kinetics involved in phosphorylation, ubiquitination, and degradation of p27 clearly demonstrate that phosphorylation of p27 at Ser-10 followed by ubiquitination and degradation is an early event as opposed to the late event observed with pp27Thr187. (arvojournals.org)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • Indeed, overexpression of D-cyclins is seen in a large number of human cancers ( 2 , 3 ). (pnas.org)
  • Pfn1 overexpression results in increased protein stability of p27 kip1 (p27 - a major cyclin-dependent kinase inhibitor) and marked elevation in the overall cellular level of p27. (pubmedcentralcanada.ca)
  • Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
  • Based on this function, p27 is described as a tumor suppressor protein. (nih.gov)
  • One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). (wikipedia.org)
  • 7 8 9 The Ser-10 site is also phosphorylated by human kinase-interacting stathmin (hKIS), 10 a nuclear serine-threonine kinase. (arvojournals.org)
  • There are currently no images for p27/Kip1 Antibody (NBP2-47771AF532). (novusbio.com)
  • Green: AF488-labeled p27 Monoclonal Antibody (SX53G8). (genetex.com)
  • Immunohistochemical staining of human ulcerative colitis tissue using anti-p27 Kip1 antibody (GTX100446). (genetex.com)
  • p27 Kip1 antibody detects p27 Kip1 protein at cytoplasm and nucleus by immunofluorescent analysis. (genetex.com)
  • Green: p27 Kip1 protein stained by p27 Kip1 antibody (GTX100446) diluted at 1:500. (genetex.com)
  • Wild-type (WT) and p27 Kip1 knockout (KO) HeLa cell extracts (30 µg) were separated by 12% SDS-PAGE, and the membrane was blotted with p27 Kip1 antibody (GTX100446) diluted at 1:500. (genetex.com)
  • p27 Kip1 antibody detects p27 Kip1 protein by Western blot analysis. (genetex.com)
  • Various whole cell extracts (30 μg) were separated by 12% SDS-PAGE, and the membrane was blotted with p27 Kip1 antibody (GTX100446) diluted at 1:1000. (genetex.com)
  • p27 protein levels do not change as serum-stimulated quiescent mouse fibroblasts progress through the cell cycle. (nih.gov)
  • Liver protein levels of p27, p21, p70 S6 kinase (p70 s6k ), phosphorylated p70 s6k ( p -p70 s6k ), eukaryotic initiation factor 4E-binding protein (4E-BP1), p -4E-BP1 (Thr37/46), and p -4E-BP1 (Ser65/Thr70) were determined by Western blotting. (aspetjournals.org)
  • p27 and p21 mRNA did not differ. (aspetjournals.org)
  • Physiological concentrations of all-trans-RA reduced the levels of cyclin E mRNA by 6 h and reduced cyclin E protein in a dose- and time-dependent manner. (ovid.com)
  • This chapter begins with general information on the role of 5'-AMP activated kinase (AMPK) in human physiology and the molecular mechanisms that control this kinase. (intechopen.com)
  • Glycogen synthase kinase 3 (GSK3) appeared to be required for survival of MLL cells in vitro and in a mouse model of the disease, reported Michael L. Cleary, M.D., of Stanford, and colleagues online in Nature . (medpagetoday.com)
  • and retinoblastoma protein (pRb), extracellular signal-regulated kinase (ERK) 1/2, and Akt phosphorylation. (ahajournals.org)
  • Promoting apoptosis: a novel activity associated with the Cyclin-dependent kinase inhibitor p27. (atcc.org)
  • After 4 h of reperfusion spinal cord biopsy samples were analyzed for neuronal damage (hematoxyline-eosine and Nissl staining), expression of the cyclin-dependent kinase inhibitor genes p21 and p27 (immunohistochemistry), and apoptosis (terminal deoxynucleotidyl transferase mediated nick end labeling assay). (springer.com)
  • Neither p21 and p27 expression nor apoptosis showed any intergroup difference. (springer.com)
  • Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in multiple endocrine neopla. (cdc.gov)
  • It has been previously reported that miRs can act as tumor oncogenes or suppressors during cancer development, dependent on the role of their target genes ( 9 - 11 ). (spandidos-publications.com)
  • One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in cell cycle, among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present. (wikipedia.org)
  • Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an inhibitor of the catalytic subunit of PI3K. (abcam.com)
  • CDK4, for instance, is positively regulated by cyclin D and can be inhibited by binding to members of the inhibitors of CDK4 (INK4) family, which act by preventing association of the CDK4 catalytic subunit to the positive regulator cyclin D1. (jneurosci.org)
  • Recombinant protein encompassing a sequence within the center region of human p27 Kip1. (genetex.com)
  • The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were specifically involved in the ubiquitination of p27. (elsevier.com)
  • First, ubiquitin is activated by the ATP-dependent formation of a thiolester bond with a conserved Cys residue of a ubiquitin-activating enzyme, E1. (plantcell.org)
  • Association of p27 with ubiquitin E3 ligase was determined with coimmunoprecipitation followed by immunoblot analysis. (arvojournals.org)
  • Interestingly, FaDu cells with reduced cortactin levels also exhibited a significant diminution in RhoA expression and activity, together with decreased expression of Skp2, a critical component of the SCF ubiquitin ligase that targets p27(Kip1) and p57(Kip2) for degradation. (garvan.org.au)
  • NSC43067 is a Cyclin-dependent kinase (Cdk) inhibitor which binds to a novel conserved site on Cdk, presumably the p27 binding pocket. (sigmaaldrich.com)
  • In the absence of p27 Kip1 , CD8 T cells showed superior recall responses shortly after vaccination with recombinant Listeria monocytogenes . (asm.org)
  • In addition, confirmation of the involvement of the proteasome-mediated proteolysis in p27 degradation should stimulate new strategies of nonsurgical treatments of non-small cell lung cancer. (aacrjournals.org)
  • We found that tumors expressing low to undetectable levels of p27 contained high p27 degradation activity. (aacrjournals.org)
  • Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p27 half-life measured in these cells. (elsevier.com)
  • The specific proteolysis of p27 may represent a mechanism for regulating the activity of cyclin-dependent kinases. (elsevier.com)
  • Because p27 plays such a key role in controlling cell division, its activity is tightly regulated. (nih.gov)
  • One model proposes that cyclin D quantities, and thus cyclin D- Cdk4 and -6 activity, gradually increases during G1 rather than oscillating in a set pattern as do S and M cyclins. (wikipedia.org)
  • Recent work exploring p21 activation in response to DNA damage at a single-cell level have demonstrated that pulsatile p53 activity leads to subsequent pulses of p21, and that the strength of p21 activation is cell cycle phase dependent. (wikipedia.org)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
  • In fact, GSK3 inhibitors could have dual activity in patients with MLL. (medpagetoday.com)
  • A) Confocal images (maximum projections, z-series of ten 1 μm steps) of anti-BrdU (red) and anti-p27 (green) immunolabeling in CV papillae of wild-type mice at 1, 3, 7 and 15 days following intraperitoneal injection of the BrdU. (biomedcentral.com)
  • Here, we have identified the cyclin-dependent kinase inhibitor p27 Kip1 as a critical regulator of the CD8 T-cell homeostasis at all phases of the T-cell response to an acute viral infection in mice. (asm.org)
  • The antiproliferative effects of K + channel blockers and veratridine were still present in OP cells isolated from INK4a −/− mice, lacking the cyclin-dependent kinase inhibitors p16 INK4a and p19 ARF . (jneurosci.org)
  • 4 A deficiency of p27 Kip1 in mice leads to benign hyperplasia in multiple organs, but it does not directly produce tumors. (ahajournals.org)
  • Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (thefreedictionary.com)
  • In the past, we and others generated cyclin D1-deficient mice and have shown that these mice display developmental abnormalities, hypoplastic retinas, and pregnancy-insensitive mammary glands. (pnas.org)
  • To test the significance of cyclin D1-p27 Kip1 interaction within a living mouse, we crossed cyclin D1-deficient mice with mice lacking p27 Kip1 , and we generated double-mutant cyclin D1 −/− p27 −/− animals. (pnas.org)
  • Here we report that ablation of p27 Kip1 restores essentially normal development in cyclin D1-deficient mice. (pnas.org)
  • We took advantage of cyclin D1-deficient mice that we and others had previously generated. (pnas.org)
  • These cyclin D1 −/− mice are viable but show developmental abnormalities and hypoplastic retinas and display mammary glands that fail to undergo normal lobuloalveolar development during pregnancy ( 7 , 8 ). (pnas.org)
  • We crossed cyclin D1-deficient mice with mice lacking p27 Kip1 ( 9 - 11 ) and generated double-mutant animals. (pnas.org)
  • Generation of Double-Mutant Cyclin D1 −/− p27 −/− Mice. (pnas.org)
  • Cyclin D1 +/− mice ( 7 , 8 ) were crossed with p27 +/− ( 11 ) mice. (pnas.org)
  • The resulting cyclin D1 +/− p27 +/− heterozygotes were bred to generate cyclin D1 −/− p27 −/− mice. (pnas.org)
  • 1996 ) A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. (biologists.org)
  • Moreover, a GSK3 inhibitor prolonged survival in mice with transplanted MLL cells, the researchers said. (medpagetoday.com)
  • Dr. Cleary and colleagues also found that when mice were implanted with MLL-type cells, treatment with oral lithium -- the same drug used for bipolar disorder, but also a weak inhibitor of GSK3 -- their survival was prolonged. (medpagetoday.com)
  • In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. (biomedcentral.com)
  • p15, p16, p21 and p27 in mouse ovaries by immunohistochemistry to assess whether the initiation of primordial follicle growth was associated with the expression of CDKIs. (biomedcentral.com)
  • In the myelomonocytic cell line, active vitamin D 3 is known to activate the transcription of both p21 and p27, cyclin-dependent kinase inhibitors (CDKIs), regulating the transition from the G 1 to the S phase of the cell cycle, in a VDR-dependent manner. (elsevier.com)
  • A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. (curehunter.com)
  • When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times ( P = 0.0012). (aacrjournals.org)
  • The possibility of a simple assay, such as the immunohistochemical analysis of p27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of patients who undergo surgical resection. (aacrjournals.org)
  • Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
  • The expression of both p21 and p27 was also significantly lower in nodular hyperplasias than in diffuse hyperplasias or normal parathyroid glands. (elsevier.com)
  • Sections of parathyroid glands with a high expression of nuclear VDR highly expressed both p21 and p27. (elsevier.com)
  • In nodular hyperplasias, the expression of both p21 and p27 correlated either positively with the nuclear VDR expression or inversely with the glandular weight. (elsevier.com)
  • Therefore, the reduced expression of p21 and p27, being VDR dependent, is a major pathogenic factor for nodular parathyroid gland growth in advanced 2HPT. (elsevier.com)
  • Cell type-specific induction of cyclin D and cyclin-dependent kinase inhibitor p27(kip1) expression by estrogen in rat endometrium. (scienceexchange.com)
  • The up-regulation of p27(kip1) is restricted to stromal cells with a 'gradient-like' expression pattern, in which the sub-epithelial (functional) layer showed stronger staining than the basal layer. (scienceexchange.com)
  • In quiescent young HDF, cyclin D1 and cyclin E are present in low amounts, but upon serum stimulation both their expression and their associated kinase activities increase during the mid and late G 1 phases, respectively ( 14 , 50 ). (asm.org)
  • Background -The cyclin-dependent kinase inhibitors (CKIs) have different patterns of expression in vascular diseases. (ahajournals.org)
  • Reportedly, low p27 expression has been associated with unfavorable prognosis in renal cell carcinoma, colon carcinoma, breast carcinomas, non-small-cell lung carcinoma, hepatocellular carcinoma, multiple myeloma, and lymph node metastases in papillary carcinoma of the thyroid, as well as a more aggressive phenotype in carcinoma of the cervix. (novusbio.com)
  • Ruiling Zhang and team from Xinxiang Medical University explored the correlation between cyclin-dependent kinase 5 expression in the hippocampus and neurological impairments following prenatal ethanol exposure, and found that prenatal ethanol exposure could affect cyclin-dependent kinase 5 and its activator p35 in the hippocampus of offspring rats. (thefreedictionary.com)
  • Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. (thefreedictionary.com)
  • p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. (biologists.org)
  • In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. (biologists.org)
  • In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. (biologists.org)
  • and upregulated expression of cyclooxygenase (COX)-2 and p27. (ahajournals.org)
  • We show that Efemp1 expression is connected to the cyclin-dependent kinase inhibitor p27(Kip1). (jove.com)
  • However, it is still controversial whether expression or loss of expression of p27 kip1 has any prognostic significance in human ovarian cancer (7-11) . (aacrjournals.org)
  • In this paper, we addressed this question by evaluating the subcellular localization of p27 kip1 and its expression using tissue microarrays from 441 patients with ovarian cancer. (aacrjournals.org)
  • The cell cycle pathways perturbed by lovastatin have been shown by several laboratories to result in the induction of CKIs p21 and/or p27 ( 16 - 21 ) independent of other standard G 1 -arresting agents/conditions such as serum starvation or double thymidine block ( 17 ). (pnas.org)
  • Involvement of p38 mitogen-activated protein kinase in basic fibroblast growth factor-induced interl. (biomedsearch.com)
  • Thus, the abundance of p27 in cells is regulated by degradation. (elsevier.com)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • The differential regulation of cyclins and p27(kip1) in the epithelium and stroma of the endometrium appear indicative of distinct actions of estrogen in different cell types in the uterus, as D-type cyclins mediate the proliferative effect of estrogen in epithelial cells while p27(kip1) might help prevent the same effect in the stroma. (scienceexchange.com)
  • Additionally, we show that p27 Kip1 constrains proliferative renewal of memory CD8 T cells, especially of the effector memory subset. (asm.org)
  • Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. (nih.gov)
  • Specifically, p27 normally blocks cells from entering the phase of the cell cycle when DNA is copied (replicated) in preparation for cell division. (nih.gov)
  • Studies suggest that p27 is also involved in controlling cell differentiation, which is the process by which cells mature to carry out specific functions. (nih.gov)
  • Cells with a shortage of functional p27 can divide too quickly or in an uncontrolled way, forming a tumor. (nih.gov)
  • studies suggest that certain endocrine cells may be particularly dependent on the p27 protein to control cell division. (nih.gov)
  • The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed in most proliferating cells and the relative amounts expressed differ in various cell types. (wikipedia.org)
  • Maspin (Mammary Serine Protease Inhibitor) was first identified in normal mammary glands and breast cancer cells. (biomedcentral.com)
  • Since TGF-βs are natural inhibitors of growth, we postulated that there may be a loss or downregulation of TGF-β in cancer cells, thereby permitting their growth. (springer.com)
  • We further showed that these two populations of p27 function at different stages of the G 1 phase of the cell cycle in response to mitogenic signals and that phosphorylation of p27 at Ser-10 is the major mechanism for the G 1 /S transition in corneal endothelial cells (CECs) in response to FGF-2 stimulation. (arvojournals.org)
  • Markers, which predict responsiveness of PDAC cells towards PI3K inhibitors are unknown. (jove.com)
  • In breast cancer, the appearance of p27 kip in the cytoplasm of tumor cells is associated with poor prognosis (3, 7) . (aacrjournals.org)
  • Two major classes of CDK inhibitors have been identified. (biomedcentral.com)
  • The purpose of this review is to provide a broad overview of the development of various classes of CDK inhibitors. (aspetjournals.org)
  • Lovastatin is an inhibitor of hydroxymethyl glutaryl (HMG)-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. (pnas.org)
  • 4 Angiotensin-converting enzyme (ACE) inhibitor suppresses neointima formation after endothelial injury in rat carotid artery and abdominal aorta. (ahajournals.org)
  • The contribution of kinins in the protective effect of angiotensin-converting enzyme (ACE) inhibitors against arterial thickening caused by balloon injury was demonstrated in rats by the use of a B 2 receptor antagonist. (ahajournals.org)
  • STANFORD, Calif., Sept. 17 -- Inhibitors of an intracellular signaling enzyme could be an effective treatment for mixed lineage leukemia (MLL), a malignancy in infants, although the strategy also has potential risk, researchers here said. (medpagetoday.com)
  • Subcellular localization of the p27 kip1 protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma. (aacrjournals.org)
  • Detects endogenous levels of p27 Kip 1 only when phosphorylated at threonine 198. (abcam.com)