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 p21
Cell Cycle Proteins
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.
Cyclin-Dependent Kinase Inhibitor p16
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.
Tumor Suppressor Proteins
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
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.
Cyclin-Dependent Kinase Inhibitor p57
Cyclin-Dependent Kinase 5
CDC2 Protein Kinase
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.
Cyclin-Dependent Kinase Inhibitor Proteins
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
Cyclin-Dependent Kinase Inhibitor p18
Tumor Suppressor Protein p53
Tumor Cells, Cultured
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.
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.
E2F1 Transcription Factor
Transcription Factor DP1
Proliferating Cell Nuclear Antigen
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.
Cyclin-Dependent Kinase Inhibitor p15
MAP Kinase Signaling System
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.
E2F Transcription Factors
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.
Molecular Sequence Data
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.
Calcium-Calmodulin-Dependent Protein Kinases
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)
Cyclin-Dependent Kinase Inhibitor p19
S-Phase Kinase-Associated Proteins
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.
Gene Expression Regulation
Protein Kinase C
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.
Reverse Transcriptase Polymerase Chain Reaction
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.
Intracellular Signaling Peptides and Proteins
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.
Amino Acid Sequence
p38 Mitogen-Activated Protein Kinases
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.
Mitogen-Activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
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.
Promoter Regions, Genetic
RNA, Small Interfering
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.
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.
Cyclic AMP-Dependent Protein Kinases
Gene Expression Regulation, Neoplastic
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)
Mitogen-Activated Protein Kinase 3
Proto-Oncogene Proteins c-akt
Recombinant Fusion Proteins
JNK Mitogen-Activated Protein Kinases
Dose-Response Relationship, Drug
Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer. (1/2420)The evolution of alterations on chromosome 9, including the putative tumor suppressor genes mapped to the 9p21-22 region (the MTS genes), was studied in relation to the progression of human urinary bladder neoplasia by using whole organ superimposed histologic and genetic mapping in cystectomy specimens and was verified in urinary bladder tumors of various pathogenetic subsets with longterm follow-up. The applicability of chromosome 9 allelic losses as non-invasive markers of urothelial neoplasia was tested on voided urine and/or bladder washings of patients with urinary bladder cancer. Although sequential multiple hits in the MTS locus were documented in the development of intraurothelial precursor lesions, the MTS genes do not seem to represent a major target for p21-23 deletions in bladder cancer. Two additional tumor suppressor genes involved in bladder neoplasia located distally and proximally to the MTS locus within p22-23 and p11-13 regions respectively were identified. Several distinct putative tumor suppressor gene loci within the q12-13, q21-22, and q34 regions were identified on the q arm. In particular, the pericentromeric q12-13 area may contain the critical tumor suppressor gene or genes for the development of early urothelial neoplasia. Allelic losses of chromosome 9 were associated with expansion of the abnormal urothelial clone which frequently involved large areas of urinary bladder mucosa. These losses could be found in a high proportion of urothelial tumors and in voided urine or bladder washing samples of nearly all patients with urinary bladder carcinoma. (+info)
Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer. (2/2420)Recent studies have shown that patients whose bladder cancer exhibit overexpression of RB protein as measured by immunohistochemical analysis do equally poorly as those with loss of RB function. We hypothesized that loss of p16 protein function could be related to RB overexpression, since p16 can induce transcriptional downregulation of RB and its loss may lead to aberrant RB regulation. Conversely, loss of RB function has been associated with high p16 protein expression in several other tumor types. In the present study RB negative bladder tumors also exhibited strong nuclear p16 staining while each tumor with strong, homogeneous RB nuclear staining were p16 negative, supporting our hypothesis. To expand on these immunohistochemical studies additional cases were selected in which the status of the p16 encoding gene had been determined at the molecular level. Absent p16 and high RB protein expression was found in the tumors having loss of heterozygosity within 9p21 and a structural change (mutation or deletion) of the remaining p16 encoding gene allele, confirming the staining results. These results strongly support the hypothesis that the RB nuclear overexpression recently associated with poor prognosis in bladder cancer is also associated with loss of p16 function and implies that loss of p16 function could be equally deleterious as RB loss in bladder and likely other cancers. (+info)
Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (3/2420)Malignant glial tumors (anaplastic astrocytomas and glioblastomas multiforme) arise mostly either from the progression of low grade precursor lesions or rapidly in a de novo fashion and contain distinct genetic alterations. There is, however, a third subset of malignant gliomas in which genetic lesions remain to be identified. Following surgical resection, all gliomas appear to have an inherent tendency to recur. Comparative molecular analysis of ten primary malignant gliomas (three anaplastic astrocytomas and seven glioblastomas multiforme) with their recurrences identified two distinct subgroups of recurrent tumors. In one group, primary tumors harbored genetic aberrations frequently associated with linear progression or de novo formation pathways of glial tumorigenesis and maintained their genetic profiles upon recurrence. In the other subset with no detectable known genetic mutations at first presentation, the recurrent tumors sustained specific abnormalities associated with pathways of linear progression or de novo formation. These included loss of genes on chromosomes 17 and 10, mutations in the p53 gene, homozygous deletion of the DMBTA1 and p16 and/ or p15 genes and amplification and/or overexpression of CDK4 and alpha form of the PDGF receptor. Recurrent tumors from both groups also displayed an abnormal expression profile of the metalloproteinase, gel A, and its inhibitor, TIMP-2, consistent with their highly invasive behavior. Delineation of the molecular differences between malignant glioblastomas and their subsequent recurrences may have important implications for the development of rational clinical approaches for this neoplasm that remains refractory to existing therapeutic modalities. (+info)
Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (4/2420)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. (5/2420)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)
Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (6/2420)The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)
Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (7/2420)We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent. (+info)
Alterations of Rb pathway (Rb-p16INK4-cyclin D1) in preinvasive bronchial lesions. (8/2420)Lung cancer results from a stepwise accumulation of genetic and molecular abnormalities with unknown temporal relationships to precursor bronchial lesions. In a search for biomarkers of malignant progression, we analyzed the expression of the tumor suppressor gene Rb and of the proteins regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1, in preinvasive bronchial lesions accompanying cancer in 75 patients, in comparison with similar lesions in 22 patients with no cancer history. Rb was constantly expressed in preinvasive lesions, including carcinoma in situ (CIS). In contrast, p16 expression was lost in moderate dysplasia (12%) and in CIS (30%) in patients with lung cancer. p16 loss occurred exclusively in patients who displayed loss of p16 expression in their related invasive carcinoma. Loss of p16 expression was not seen in nine patients with dysplasia but no cancer progression. Cyclin D1 overexpression was seen in hyperplasia and metaplasia (6%), mild dysplasia (17%), moderate dysplasia (46%), and CIS (38%) in patients with cancer but was lost in 5% of the patients during the process of invasion; it was also observed in patients with no cancer progression (14%). Our results indicate that Rb protein function can be invalidated before invasion through alteration of the Rb phosphorylation pathway, by p16 inhibition, and/or by cyclin D1 overexpression and suggest a role for p16 and cyclin D1 deregulation in progression of preinvasive bronchial lesions to invasive carcinoma. (+info)
Cyclin-dependent kinase inhibitor protein
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 ( ...
"CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". U.S. National Library of Medicine. Archived from ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... a low-molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) - which has been localised to the p21 ... BRAF inhibitors, such as vemurafenib and dabrafenib and a MEK inhibitor trametinib are the most effective, approved treatments ...
... is also known as: p16INK4A p16Ink4 Cyclin-dependent kinase inhibitor 2A (CDKN2A) CDKN2 CDK 4 Inhibitor Multiple Tumor ... p16 is an inhibitor of cyclin-dependent kinases (CDK). It slows down the cell cycle by prohibiting progression from G1 phase to ... "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". Nobori T, Miura K, Wu DJ, Lois A, ... p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other ...
The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ... Rivera-Torres J, José ES (2019). "Src Tyrosine Kinase Inhibitors: New Perspectives on Their Immune, Antiviral, and ...
Meis1 has been shown to be necessary for the activation of the cyclin-dependent kinase inhibitors p15, p16, and p21. Knockout ... Cyclin-dependent kinases and cyclin-dependent kinase inhibitors play key roles in this process. One gene, jumonji (jmj), has ... Cardiomyocytes have been shown to be encouraged to exit the cell cycle then cyclin-dependent kinases are downregulated, or when ... of the cardiomyocyte cell cycle is believed to be regulated by transcription factors and cyclin dependent kinase inhibitors, ...
Cyclin-dependent kinase inhibitor p16, a cell-cycle inhibitor; MGMT, a DNA repair gene; APC, a cell cycle regulator; MLH1, a ... For example, hypermethylation of the genes coding for Death-Associated Protein Kinase (DAPK), p16, and Epithelial Membrane ... Histone deacetylase (HDAC) inhibitors show efficacy in treatment of T cell lymphoma. two HDAC inhibitors, vorinostat and ... Treatment with HDAC inhibitors has been found to promote gene reactivation after DNA methyl-transferases inhibitors have ...
As a cyclin-dependent kinase inhibitor (CDKI), p16 works by down-regulating molecules that keep pRB in an active, ... The p16-pRB pathway can be activated by the DNA Damage Response, but is usually secondary to the p53 response in such cases. ... In addition, p16 expression has been shown to increase with age in the mouse brain, bone marrow and pancreas. Senescent cells ... Telomere-dependent senescence is caused by the shortening of telomeres due to the end-replication problem of DNA replication. ...
This protein belongs to the CDKN2 cyclin-dependent kinase inhibitor family. p16 comprises four ankyrin repeats, each spanning a ... "Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene ... When working normally, p16 binds to the cyclin dependent kinases CDK4 to inhibit their ability to create tumors, but when ... p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ...
Cyclin-dependent kinase 4
"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. ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (Oct 2002). "The human and mouse replication-dependent histone genes". ... 1999). "Cloning and characterization of RLPK, a novel RSK-related protein kinase". J. Biol. Chem. 274 (2): 1026-32. doi:10.1074 ... the CDK-activating kinase". J. Biol. Chem. 270 (31): 18195-7. doi:10.1074/jbc.270.31.18195. PMID 7629134. Albig W, Drabent B, ...
Disposable soma theory of aging
Lastly, studies have also indicated that the mTOR pathway also alters immune responses and stimulates cyclin-dependent kinase ( ... CDK) inhibitors such as p16 and p21. This leads to alteration of the stem-cell niche and results in stem cell exhaustion, ... Mechanistically, the NAD-dependent deacetylase Sirtuin 1 (SIRT-1) is upregulated during low-nutrient periods. SIRT-1 increases ... This cascade results in kinases phosphorylating forkhead transcription factor (FOXO), deactivating it. Deactivation of FOXO ...
... is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, ... P16 is formed from four ankyrin repeat (AR) motifs that exhibit a helix-turn-helix conformation except that the first helix in ... Ortega S, Malumbres M, Barbacid M (March 2002). "Cyclin D-dependent kinases, INK4 inhibitors and cancer". Biochimica et ... cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4))". Atlas of genetics and cytogenetics in oncology and haematology. ...
"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 ...
Cyclin-dependent kinase 7
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...
"Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on ... CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ...
"Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ... Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... Yang W, Zhang A, Han Y, Su X, Chen Y, Zhao W (2021). "Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional ...
2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27( ... Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene. The protein encoded by this ... "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)". Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, ... 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ...
HPV-positive oropharyngeal cancer
CDKN2A is a tumour suppressor gene that encodes a tumor suppressor protein, p16 (cyclin-dependent kinase inhibitor 2A) and ... inhibits the kinase activity of the cyclin-dependent kinases CDK4 and CDK6, which in turn induce cell cycle arrest. p16 ... "Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal ... High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response. The risk of ...
... which leads to the increase in the synthesis of the selective cyclin-dependent kinase (CDK) inhibitor proteins, p12 and p16. ... OGF receptor axis uses the p16 pathway to inhibit head and neck cancer". Cancer Research. 67 (21): 10511-8. doi:10.1158/0008- ...
"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 ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... P16 functions in inactivating cyclin D/Cdk 4 complex. Thus, blocking transcription of INK4 gene would increase cyclin D/Cdk4 ... 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 ...
Cyclin-dependent kinase 6
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... 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 ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ...
The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and ... CDK inhibitors. The protein encoded by this gene is a member of the cyclin family and contains the cyclin box. The encoded ... CCNG1 has been shown to interact with: Mdm2, P16, P53, and PPP2R4. GRCh38: Ensembl release 89: ENSG00000113328 - Ensembl, May ... "Cyclin G1 and cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell cycle-regulated expression ...
... cyclin E and cyclin A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule ... Furthermore, triple knockout, p16 addition, and Cdk 4/6 inhibitor addition experiments confirmed that Cyclin D- Cdk 4/6 is the ... When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases (CDK) and cyclins phosphorylate pRb, ... One such example of E2F-regulated genes repressed by pRb are cyclin E and cyclin A. Both of these cyclins are able to bind to ...
Cell cycle checkpoint
At this point, E2F 1-3 proteins bind to DNA and transcribe Cyclin A and Cdc 6. Cyclin-dependent kinase inhibitor 1B (CDKN1B), ... p16 disrupts cyclin D-CDK4 complexes, thus causing the release of p21 from the complexes, which leads to the dephosphorylation ... 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 ...
Delmer A, Tang R, Senamaud-Beaufort C, Paterlini P, Bréchot C, Zittoun R. Alterations of cyclin kinase 4 inhibitor (p16 INK4A/ ... Caspase-dependent alterations of Ca2+ signaling in the induction of apoptosis by Hepatitis B virus X protein. J Biol Chem. 278 ... Paterlini, P., Flejou, J-F., De Mitri, M.S., Pisi, E., Franco, D., Bréchot, C. Structure and expression of the Cyclin A gene in ... Paterlini, P., De Mitri, S., Martin, C., Munnich, A., Bréchot, C., A TaqI polymorphism in the human cyclin A gene. In Nucleic ...
The cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors ( ... Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of the Ink family of inhibitors (p15, p16, p18, and p19), ... hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in ... However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 ...
"A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer". ... Additionally, CDK4/6 and CDK2 are also inactive because CDK4/6 are bound by INK4 family members (e.g., p16), limiting kinase ... 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 ...
List of MeSH codes (D12.776)
... 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 p27 MeSH D12.776.624.776.355.700 - cyclin-dependent kinase inhibitor p57 See List of MeSH ... 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 D12.7184.108.40.2060.500 - cdc2 protein ...
Cyclin D-1 is a regulator of cyclin-dependent kinases (CDK4 and CDK6). It has been shown to interact with the retinoblastoma ... Tyrosine kinase Inhibitors block the action of these enzymes. Tyrosine kinase inhibitors have been shown to inhibit the VEGF, ... It is modified to selectively replicate in p16/Rb-defective cells, which include most human cancer cells. In addition, CGTG-102 ... with cyclin D1 CDK inhibitors are being studied. palbociclib is a CDK inhibitor (approved for some breast cancer). Other ...
Index of biochemistry articles
... cyclin - cyclin A - cyclin B - cyclin E - cyclin-dependent kinase - cycloleucine - cyclosporin - cyclosporine - cystatin - ... inhibitor - inhibitory gi G-protein - Inorganic chemistry - insect protein - Insulin - insulin receptor - insulin-like growth ... protein P16 - protein P34cdc2 - protein precursor - protein structure prediction - protein subunit - protein synthesis - ... ribosomal protein S6 kinase - ribosome - RNA - RNA virus - RNA-binding protein - RNA-directed DNA polymerase - rod outer ...
SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclins E/D, respectively, ... Ben-Saadon R, Fajerman I, Ziv T, Hellman U, Schwartz AL, Ciechanover A (October 2004). "The tumor suppressor protein p16(INK4a ... This is achieved by continuous control of cyclins or CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ...
The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... and CDKN2A/p16 in colorectal adenomas". World Journal of Gastroenterology. 16 (28): 3553-60. doi:10.3748/wjg.v16.i28.3553. PMC ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ...
Inhibitors of the MDM2-p53 interaction include the cis-imidazoline analog nutlin. Levels and stability of Mdm2 are also ... Honda R, Yasuda H (March 2000). "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger ... This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high. ... Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ...
"Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". The ... Ababneh M, Götz C, Montenarh M (May 2001). "Downregulation of the cdc2/cyclin B protein kinase activity by binding of p53 to ... Pifithrin, an inhibitor of P53 italics are used to denote the TP53 gene name and distinguish it from the protein it encodes ... P16, PARC, PARP1, PIAS1, CDC14B, PIN1, PLAGL1, PLK3, PRKRA, PHB, PML, PSME3, PTEN, PTK2, PTTG1, RAD51, RCHY1, RELA, Reprimo[ ...
Detailed computational study of p53 and p16: using evolutionary sequence analysis and disease-associated mutations to predict...
Here we refine these evolutionary studies and expand them to the p16/Ink4a … ... Cyclin-Dependent Kinase Inhibitor p16 * Tumor Suppressor Protein p14ARF * Tumor Suppressor Protein p53 ... Here we refine these evolutionary studies and expand them to the p16/Ink4a gene. We calculated that in order for absolute ... We calculated p16 evolution using amino acid substitution matrices and nucleotide substitution distances. We looked for ...
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line...
... whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or ... Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer. Mangini NS, ... The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line ... The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line ...
CDKN2A gene: MedlinePlus Genetics
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4). *cyclin-dependent kinase inhibitor 2A isoform p12 ... and pancreatic cancers in addition to melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A mutation: ... cyclin-dependent kinase inhibitor 2A isoform p14ARF. *cyclin-dependent kinase inhibitor 2A isoform p16gamma ... cyclin-dependent kinase 4 inhibitor A. *cyclin-dependent kinase inhibitor 2A. * ...
DeCS 2006 - Changed terms
Low mutation burden and frequent loss of CDKN2A/B and SMARCA2, but not PRC2, define premalignant neurofibromatosis type 1...
Cyclin-Dependent Kinase Inhibitor p16/genetics; Cyclin-Dependent Kinase Inhibitor p16/metabolism; Cyclin-Dependent Kinase ... Inhibitor p21/genetics*; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Disease Models, Animal; Doxorubicin/pharmacology; ... also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in ... Plasminogen Activator Inhibitor 1/deficiency; Plasminogen Activator Inhibitor 1/genetics*; RNA, Small Interfering/genetics; RNA ...
9. Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in and highly specific to lymphoid tumors in ... 4. Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute ... Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.. Hayette S; Thomas X; Bertrand Y; Tigaud I; ... MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme.. Moulton T; Samara G; Chung WY; Yuan L; Desai R; Sisti M; Bruce J; ...
... p16) is a biomarker being researched by EDRN ... p16) is a biomarker being researched by EDRN ... Cyclin-dependent kinase 4 inhibitor A. *Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 ... Hypermethylation of p16 gene promoter correlates with loss of p16 expression that results in poorer prognosis in esophageal ... two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript ...
Cyclin-Dependent Kinase Inhibitor p16 [D12.776.624.776.355.200] * Cyclin-Dependent Kinase Inhibitor p18 [D12.776.624.776. ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.644.360.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.644.360.225.100] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.167.187] * Cyclin-Dependent Kinase Inhibitor p15 [D12.7220.127.116.11] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.476.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.776.476.225.100] ...
RFA-DE-04-003: MOLECULAR ANATOMY OF HEAD & NECK CANCER: A GENOMIC/PROTEOMIC APPROACH
Latest News and Comment
Targeting cyclin-dependent kinase 4 (CDK4) and CDK6 increases endocrine therapy efficacy, leading to the approval of CDK4/6 ... HPV DNA and p16INK4a positivity in vulvar cancer and vulvar intraepithelial neoplasia - Authors reply. The Lancet Oncology ... inhibitors palbociclib, ribociclib, and abemaciclib in the this treatment setting.1. *. Correspondence ... HPV DNA and p16INK4a positivity in vulvar cancer and vulvar intraepithelial neoplasia. The Lancet Oncology ...
Cyclin-Dependent Kinase Inhibitor p16 [D12.776.624.776.355.200] * Cyclin-Dependent Kinase Inhibitor p18 [D12.776.624.776. ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.644.360.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.644.360.225.100] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.167.187] * Cyclin-Dependent Kinase Inhibitor p15 [D12.718.104.22.168] ... Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.476.225] * Cyclin-Dependent Kinase Inhibitor p15 [D12.776.476.225.100] ...
Pesquisa | Prevenção e Controle de Câncer
CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CFB: complement factor B; DELEC1/Dec1; deleted in esophageal cancer 1; ... However, MG-132 is a non-selective proteasome inhibitor. In this study, we used the selective proteasome inhibitor epoxomicin ... In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects ... In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 ...
Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and...
臺北醫學大學癌症轉譯研究中心 - 研究
Cyclin-Dependent Kinase Inhibitor p16 100% * Paclitaxel 68% * Computational Biology 64% * Adenocarcinoma 53% ... Cancer and mTOR inhibitors in kidney transplantation recipients. Kao, C. C., Liu, J. S., Chang, Y. K., Lin, M. H., Lin, Y. C., ... Brutons tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma. Yeh, C. T., Chen, T. T. ... Calcium-dependent up-regulation of mitochondrial electron transfer chain gene expressions in human luteinized granulosa cells. ...
Cyclin Dependent Kinase Inhibitor 2A Cyclin Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor-2A INK4A Protein ... Cyclin Dependent Kinase Inhibitor 2A. Cyclin Dependent Kinase Inhibitor p16. Cyclin-Dependent Kinase Inhibitor-2A. INK4A ... Cyclin-Dependent Kinase Inhibitor p16 - Preferred Concept UI. M0029615. Scope note. A product of the p16 tumor suppressor gene ... Cyclin-Dependent Kinase Inhibitor p16 Descriptor Spanish: Inhibidor p16 de la Quinasa Dependiente de Ciclina Spanish from Spain ...
Outcome Parameters List | AlzPED
D C177536 GDC Property Terminology C127771 Tumor Cell to Total Cell Ratio Measurement The determination of the ratio of tumor...
... or cyclin-dependent kinase inhibitor-2A (p16). Tumor cell selectivity is achieved through a 24-base pair deletion in the E1A ... small molecule inhibitor of the receptor tyrosine kinases anaplastic lymphoma kinase (ALK), C-ros oncogene 1 (ROS1) and Met ( ... a polo-like kinase 4 (PLK4) inhibitor with potential antineoplastic activity. Upon oral administration, polo-like kinase 4 ... small molecule inhibitor of select serine-threonine kinases, including aurora kinase B (aurora B), vascular endothelial growth ...
Cervical cytology and HPV in cervical cancer screening: Current and future perspectives Bakshi P, Agarwal P, Mangla G - Curr...
One of the most established biomarkers is p16INK4a (p16), a cyclin-dependent kinase inhibitor and essentially a regulator of ... in a dual stain p16/Ki67 has been proposed to enhance the analytical specificity of p16. It has shown utility as a triage tool ... Bergeron C, Schmidt D, Ikenberg H, Ridder R. High sensitivity and specificity of p16/Ki-67 dual stained cytology for high grade ...
Genetic methylation and lymphoid malignancies: biomarkers of tumor progression and targeted therapy | Biomarker Research | Full...
Drexler HG: Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human ... Phase I study of a novel oral janus kinase 2 inhibitor, SB1518, in patients with relapsed lymphoma: evidence of clinical and ... Differential effect of epigenetic alterations and genomic deletions of CDK inhibitors [p16(INK4a), p15(INK4b), p14(ARF)] in ... Small molecule inhibitors of WNT cascade (CGP049090 and PKF115-584) were tested in CLL. These inhibitors efficiently induce CLL ...
Antioxidants | Free Full-Text | Canagliflozin Delays Aging of HUVECs Induced by Palmitic Acid via the ROS/p38/JNK Pathway
In summary, our study revealed a new role for CAN as one of the sodium-dependent glucose transporter 2 inhibitors in delaying ... Canagliflozin (CAN), a sodium-glucose cotransporter inhibitor, can exert a cardiovascular protection effect that is likely ... a cyclin-dependent kinase inhibitor, tumor suppressor and biomarker of aging, is another major mediator for cellular senescence ... a-d) CAN (5 μg/mL) reduced PA-induced elevation of cell cycle regulators p21, p53 and p16. (e,f) CAN (5 μg/mL) ameliorated PA- ...
MCM4 - hpluswiki
Furthermore, HSYA significantly decreased the mRNA and protein level of cyclin-dependent kinase inhibitor p16, followed by ... These age-dependent changes in MCM2-7, a protein complex that directly affects cellular DNA replication, may play a critical ... mRNA levels of genes regulated by p16-Rb pathway were determined by quantitative real-time PCR. In vivo, HSYA improved the ... The expression levels of p16, CDK4, CDK6 and phosphorylation levels of Retinoblastoma (Rb) were detected by ...
Journal of Otolaryngology and Ophthalmology of Shandong University
Objective: To observe the expression of cyclindependent kinase4(CDK4) and cyclindependent kinase inhibitor P16 in human ... Result: CDK4 and P16 were expressed in parabasal layers and the upper layer, mainly in the prickle and granular layers of ... Expression of CDK4 and P16 in human middle ear cholesteatoma WU Rui-shan,HUANG Fang,YANG Jin-song JOURNAL OF SHANDONG ... All specimens were stained by an immunohistochemical SABC method to detect the expression of CDK4 and P16. Correlations between ...
Bayesian refinement of association signals for 14 loci in 3 common diseases. - CAMS Oxford Institute
Browsing by Subject "Lymphoma"
The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression ... protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin ... of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by ... ...
REPLACED MEDICAL SUBJECT HEADINGS WITH REPLACED-BY HEADINGS - 2006
Protein p16  MH NEW = Cyclin-Dependent Kinase Inhibitor p16 MH OLD = Protein p53  MH NEW = Tumor Suppressor Protein p53 MH ... CDK9 Protein Kinase  MH NEW = Cyclin-Dependent Kinase 9 MH OLD = Callimiconinae [N] MH NEW = Callimico MH OLD = ... Sodium Chloride Symporter Inhibitors MH OLD = Dosage Compensation (Genetics) [P] MH NEW = Dosage Compensation, Genetic MH OLD ...
Sean Pitroda's research topics | Profiles RNS
Control of cellular senescence by CPEB
Animals; Blotting, Western; Cell Aging; Cell Cycle; Cell Cycle Proteins; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p16 ... The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine ... The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the ... We conclude that activation of the Raf/MAP kinase pathway alone in these cells is insufficient to cause disassembly of Sos from ...
Total body irradiation selectively induces murine hematopoietic stem cell senescence. | Profiles RNS
Immunohistochemical assessment of the MIB, CK-14, p63, p16, Cal A, and Cys A markers in spindle cell squamous cell carcinomas...
... which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). ... known as cyclin-CDK complex inhibitors (CKIs)29, which includes p16. Functional loss of this gene may be associated with ... Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which ... In this study, there was no expression of p16 in 93% of cases, which confirms the hypothesis that p16 is a tumor suppressor ...
- Here we refine these evolutionary studies and expand them to the p16/Ink4a gene. (nih.gov)
- The most well-studied are the p16(INK4A) and the p14(ARF) proteins. (medlineplus.gov)
- The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. (medlineplus.gov)
- However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. (medlineplus.gov)
- In this way, p16(INK4A) controls cell division. (medlineplus.gov)
- Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division. (medlineplus.gov)
- Most of these mutations lead to production of little or no functional p16(INK4A) protein. (medlineplus.gov)
- Without p16(INK4A) to regulate cell growth and division (proliferation), cells can continue to grow and divide without control, which can lead to tumor formation. (medlineplus.gov)
- A different type of alteration involving the CDKN2A gene can result in reduced amounts or an absence of the p16(INK4A) or p14(ARF) protein. (medlineplus.gov)
- This alteration, known as promoter hypermethylation, turns off the production of p16(INK4A) or p14(ARF). (medlineplus.gov)
- The CDKN2A gene mutations found in melanoma result in a nonfunctional p16(INK4A) protein. (medlineplus.gov)
- CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
- 4. Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood. (nih.gov)
- High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families. (cdc.gov)
- In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16 INK4A and P21 Cip and reduction of E2F activity. (biomedcentral.com)
- In Rb -null hepatocytes, cMYC activity decreased slightly but P16 INK4A was not activated and the great majority of cells continued cycling. (biomedcentral.com)
- 16. Infrequent mutations and no methylation of CDKN2A (P16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan. (nih.gov)
- 12. Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma. (nih.gov)
- At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. (nih.gov)
- In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. (nih.gov)
- The expression levels of p16, CDK4 , CDK6 and phosphorylation levels of Retinoblastoma (Rb) were detected by immunohistochemistry and western blot analysis. (transhumanist.ru)
- Furthermore, HSYA significantly decreased the mRNA and protein level of cyclin-dependent kinase inhibitor p16, followed by increasing CDK4 /6 protein expression and decreasing the phosphorylation of Retinoblastoma (pRb) which up-regulated the expression of downstream genes CCNE1 , CCNA2 , P107 and MCM4 . (transhumanist.ru)
- The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
- Figure11 C and D). Figure 1 Immunocytochemistry analysis of the effects of tachyplesin on the protein levels of mutant p53, p16, cyclin D1, CDK4 in SMMC-7721 cells ( 536). (cancerhugs.com)
- The protein levels of mutant p53 (A), cyclin D1 (E), CDK4 (G) were high in SMMC-7721. (cancerhugs.com)
- 7. Homozygous loss of the MTS1/p16 and MTS2/p15 genes in lymphoma and lymphoblastic leukaemia cell lines. (nih.gov)
- 8. Homozygous deletions of p16/MTS1 and p15/MTS2 genes are frequent in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood. (nih.gov)
- 15. Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia. (nih.gov)
- A product of the p16 tumor suppressor gene ( GENES, P16 ). (nih.gov)
- mRNA levels of genes regulated by p16-Rb pathway were determined by quantitative real-time PCR. (transhumanist.ru)
- Conclusão: Os resultados suportam a investigação revelando que os genes MIG, CK14, p63, Cal A e Cys A se apresentam fortemente evidentes nos tumores de cavidade oral e o p16 suprimido, sugerindo que esta proteína pode exercer um papel de regulador negativo do ciclo celular. (bvsalud.org)
- These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. (umassmed.edu)
- PLK4, a member of the polo family of serine/threonine kinases overexpressed in a variety of cancer cell types, plays a crucial role in the regulation of centriole duplication during the cell cycle. (nih.gov)
- therapeutic_agents C1909 therapeutic_agents C C177537 GDC Value Terminology C115970 Ibcasertib An orally available, small molecule inhibitor of select serine-threonine kinases, including aurora kinase B (aurora B), vascular endothelial growth factor receptors (VEGFRs), stem cell factor receptor (c-KIT), and platelet-derived growth factor receptors (PDGFRs), with potential antineoplastic activity. (nih.gov)
- serine/threonine kinases that relay DNA damage signals to cell cycle checkpoints. (nih.gov)
- 17. MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme. (nih.gov)
- 19. p16 gene homozygous deletions in acute lymphoblastic leukemia. (nih.gov)
- This protein is produced from the alpha mRNA transcript of the p16 gene. (nih.gov)
- Both p16 gene products have tumor suppressor functions. (nih.gov)
- One of the most common genetic changes that occurs early in the progression of these tumors is loss of chromosomal region 9p21, whose main effect is inactivation of the p16 tumor suppressor gene, an inhibitor of cyclin-dependent kinase. (nih.gov)
- Other changes include a mutation in the p53 gene in half the cases, resulting in the progression from pre-invasive to invasive lesions and amplification of the cyclin D1 oncogene observed in about a third of primarily invasive tumors. (nih.gov)
- The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (affbiotech.com)
- This in turn allows the assembly of the DREAM complex-a key effector responsible for repression of cell-cycle-dependent gene expression [ 27 ]. (beds.ac.uk)
- HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. (nih.gov)
- The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. (umassmed.edu)
- Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. (biomedcentral.com)
- The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transd. (biomedcentral.com)
- The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a large family of ligands that signal through a class of cell-surface tyrosine kinase receptors. (biomedcentral.com)
- ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. (biomedcentral.com)
- In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs. (nih.gov)
- Collectively, these data indicated that HSYA could ameliorate aging, especially hepatic replicative senescence resulting from D-gal, the mechanism could be associated with the suppression of p16-Rb pathway. (transhumanist.ru)
- These age-dependent changes in MCM2 -7, a protein complex that directly affects cellular DNA replication, may play a critical role in cellular senescence. (transhumanist.ru)
- Zeb expression inhibits activation of p16 negating senescence following EGRFR overexpression. (nih.gov)
- EGCG may also interact with the mechanistic target rapamycin (MTOR) and unc-51-like autophagy activating kinase (ULK1) to modulate the interplay between autophagy and apoptosis. (bvsalud.org)
- Upon oral administration, polo-like kinase 4 inhibitor CFI-400945 selectively inhibits PLK4, which results in the disruption of mitosis and the induction of apoptosis. (nih.gov)
- Additionally, quercetin limited aHSC proliferation by inducing a G1 arrest as evidenced by decreased expression of cyclin D1、D2、A、B1、E. Moreover quercetin and gallic acid induced aHSC apoptosis via Fas/Fas ligand-mediated extrinsic pathway. (ncl.edu.tw)
- therapeutic_agents C1909 therapeutic_agents C C177537 GDC Value Terminology C128288 Luvixasertib An orally bioavailable, selective inhibitor of the dual specificity protein kinase TTK (monopolar spindle 1 kinase, Mps1), with potential antineoplastic activity. (nih.gov)
- Upon oral administration, ibcasertib binds to and inhibits the activity of aurora B, VEGFRs, c-kit and PDGFRs, which may result in a decrease in the proliferation of tumor cells that overexpress these kinases. (nih.gov)
- In addition, this agent binds to the CD40 antigen present on the surfaces of tumor cells, which induces antibody-dependent cytotoxicity (ADCC), and eventually inhibits the proliferation of CD40-expressing tumor cells. (nih.gov)
- This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. (nih.gov)
- a protein kinase that inhibits Cdk1. (nih.gov)
- Increased prevalence of lung, breast, and pancreatic cancers in addition to melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A mutation: implications for genetic counseling. (cdc.gov)
- My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. (umassmed.edu)
- In Rb -deficient cells however, p53 but not p21 Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. (biomedcentral.com)
- and phosphatidylinositol 3-kinase/Akt pathway ( Rawat and Bouchard, 2015 ), to benefit virus replication. (molcells.org)
- Cystatin A (Cys A), a cysteine protease inhibitor, is a precursor of proteins involves in keratinocyte keratinization, and is expressed during the late phase of differentiation of these cells. (bvsalud.org)
- Functional loss of p16 may lead to uncontrolled cell proliferation 3,4 . (bvsalud.org)
- The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. (umassmed.edu)
Cell cycle arrest2
- Despite the small p16 sequence database, our calculations of high conservation correctly predicted loss of cell cycle arrest function in 75% of tested codons, and low conservation correctly predicted wild-type function in 80-90% of codons. (nih.gov)
- In order for cell cycle arrest to differentiation, it is necessary either to downregulate positive regulation of CDKs, such as cyclins, or to activate negative regulators of CDKs, such as CDK inhibitors (CKIs). (cancerhugs.com)
- Cyclins function as regulators of CDK kinases. (affbiotech.com)
- Cyclin A:Cdc2 binds ORC and phosphorylates ORC2p in Xenopus (PMID: 10660590). (nih.gov)
- Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. (beds.ac.uk)
- The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal transduction pathw. (biomedcentral.com)
- This activation was blocked by expression of the MAP kinase phosphatase MKP-1. (umassmed.edu)
- This dysregulation of the stem cell pool is associated with a decreased expression of the cell cycle inhibitor p21. (biologists.com)
- Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (affbiotech.com)
- Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which suggests that the latter protein may play a role in negative regulation of cell cycle progression. (bvsalud.org)
- The current knowledge of cell cycle regulation have revealed SNS-314 that the progression of the cell cycle is governed mainly by the activation and deactivation of cyclin-dependent kinases (CDKs). (cancerhugs.com)
- A29: Cdk2 can bind either Cyclin A or Cyclin E. For details on activation of Cdk2 (PMID: 10436023). (nih.gov)
- Table 1 Effects of 3.0 mg/L tachyplesin on the cell cycle kinet-ics of SMMC-7721 cells Effects of tachyplesin on p53, p16 protein levels in SMMC-7721 cells It has revealed that p53 protein detected by immunohistochemistry is mutant p53. (cancerhugs.com)
- Cyclin D1 Antibody detects endogenous levels of total Cyclin D1. (affbiotech.com)
- A30: Cdc2 (Cdk1), in association with either Cyclin B or Cyclin A, phosphorylates ORC2. (nih.gov)
- The current p16 evolutionary substitution database is too small to determine whether observations of 'absolute conservation' are statistically significant. (nih.gov)