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)
Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1 | PNAS
The DMP1 transcription factor binds to a single consensus site in the mouse ARF promoter to activate gene expression. Mutation of this binding site abolished DMP1-stimulated expression of a reporter gene driven by a DNA fragment containing residues −225 to +56 of the ARF promoter. Conversely, a DMP1 point mutant that no longer binds to DNA was transcriptionally inert. Ets1 and Ets2 transcription factors can also bind to short oligonucleotides containing the DMP1 consensus binding site, but five Ets family members were unable to activate reporter gene expression driven by the larger 281-bp ARF promoter fragment, suggesting that DMP1 may be the preferred regulator in this context. We have seen similar effects with the promoter of the aminopeptidase-N/CD13 gene on which DMP1-DNA complexes were significantly more stable than those containing Ets factors (32). In agreement with these findings, ectopic expression of DMP1 in wild-type MEF strains induced expression of the p19ARF protein and caused ...
Studies suggest that Hsf4 expression correlates with its role in cell growth and differentiation. However, the role of Hsf4 in tumorigenesis in vivo remains unexplored. In this article, we provide evidence that absence of the Hsf4 gene suppresses evolution of spontaneous tumors arising in p53- or Arf-deficient mice. Furthermore, deletion of hsf4 alters the tumor spectrum by significantly inhibiting development of lymphomas that are normally observed in the majority of mice lacking p53 or Arf tumor suppressor genes. Using mouse embryo fibroblasts deficient in the hsf4 gene, we have found that these cells exhibit reduced proliferation that is associated with induction of senescence and senescence-associated β-galactosidase (SA-β-gal). Cellular senescence in hsf4-deficient cells is associated with the increased expression of the cyclin-dependent kinase inhibitors, p21 and p27 proteins. Consistent with the cellular senescence observed in vitro, specific normal tissues of hsf4−/− mice and ...
Cellular Senescence - QIAGEN
Senescent cells are cells that no longer divide. These cells acquire a large and flat cellular appearance, decrease contacts with other cells, and increase adhesion to the extracellular matrix. In normal replicative senescence, the cell simply enters senescence after a certain number of replications. However, stress-induced senescence causes cells to initiate senescence prematurely due to a variety of stresses. In fact, some hypothesize that the senescence program originally evolved as an antiviral mechanism. This burgeoning field may also yield other important clues about the cellular biology of aging. Molecularly, the cellular senescence program activates p53 and pRb signaling, leading to withdrawal from the cell cycle. Stress pathways that may cause cellular senescence include DNA damage, oxidative stress, interferon-related responses, and signaling via either insulin growth factors (IGF) or mitogen activated protein kinases (MAPK). Due to cellular senescence activation in early stage cancers ...
p16 INK4a Can Initiate an Autonomous Senescence Program
The tumor suppressor p16INK4a is a potent mediator of cell cycle arrest in transient expression studies, is induced in senescing cells, and can impose morphological features of senescence. Nonetheless, it is unclear whether p16INK4a can block cell proliferation irreversibly. We explored this issue u …
ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression...
The INK4a-ARF locus encodes two unrelated proteins that both function in tumor suppression. p16INK4 binds to and inhibits the activity of CDK4 and CDK6, and ARF arrests the cell cycle in a p53-dependent manner. We show here that ARF binds to MDM2 and promotes the rapid degradation of MDM2. This inte …
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How to Remove Ink From Printed Cards | eHow
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Biomolecules | Free Full-Text | Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression
Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma; head and neck squamous cell carcinomas; lung, breast, and pancreatic cancers. In melanoma, loss of function CDKN2A alterations have been identified in approximately 50% of primary melanomas, in over 75% of metastatic melanomas, and in the germline of 40% of families with a predisposition to cutaneous melanoma. The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. In this review, we describe the frequency and types of somatic alterations affecting the CDKN2A locus in melanoma and germline CDKN2A alterations in
CDKN2A (9p21.3) Orange+ 9q21.11 - Biocare Medical
The CDKN2A (9p21.3) Orange 9q21.11 Green probe is designed to detect copy number variations located on the 9p21.3 locus on chromosome 9, including the tumor suppressor gene CDKN2A. The CDKN2A gene, also known as the p16 gene has been implicated in numerous cancers1. The CDKN2A (p16) gene encodes a cyclin dependent kinase inhibitor protein and functions as a cell cycle regulator1. Gene aberrations involving the CDKN2A gene such as gene deletion and mutation are commonly identified in various cancers1, 2. Homozygous deletion of CDKN2A results in the inactivation of its gene function and is considered one of the mechanisms that drive leukemogenesis2. Furthermore, a multiplicity of solid tumors such as lung, glioma, bladder, pancreatic, and renal cancers contain CDKN2A deletions3. The high prevalence of CDKN2A gene deletions in variety of cancers, make it a viable cytogenetic target1. Conventional cytogenetic techniques such as fluorescent in situ hybridization (FISH) can be used to detect CDKN2A deletions.
Quantitative assessment of aberrant P16INK4a methylation in ovarian ca | CMAR
Quantitative assessment of aberrant P16INK4a methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets Jie Ruan,1,* Peipei Xu,2,3,* Wei Fan,4 Qiaoling Deng,3 Mingxia Yu3 1Key Laboratory for Medical Molecular Diagnostics of Guangdong, Guangdong Medical University, Dongguan, Guangdong, 523808, China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450072, China; 3Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China *These authors contributed equally to this work Abstract: Epigenetic alteration of P16INK4a is conventionally thought to induce the initiation of carcinoma. However, the role of P16INK4a methylation in ovarian cancer still remains controversial. Therefore, we performed a meta-analysis to further elucidate the relationship between P16INK4a promoter methylation and
Patent US6536874 - Symmetrically actuated ink ejection components for an ink jet printhead chip - Google Patents
A printhead chip for an ink jet printhead includes a substrate. A plurality of nozzle arrangements is positioned on the substrate. Each nozzle arrangement has an active ink ejection structure that is positioned on the substrate and spaced from the substrate. The active ink ejection structure has a roof with an ink ejection port defined in the roof. A static ink ejection structure is positioned on the substrate. The active ink ejection structure and the static ink ejection structure together define a nozzle chamber in fluid communication with an ink supply. The active ink ejection structure is displaceable with respect to the static ink ejection structure towards and away from the substrate to reduce and increase a volume of the nozzle chamber to eject an ink drop from the nozzle chamber. At least two actuators are operatively arranged with respect to the active ink ejection structure to displace the active ink ejection structure with respect to the static ink ejection structure towards and away from the
Identification of Molecular Determinants of Cellular Senescence in Cancer and Aging
Cellular senescence is a fundamental cell fate playing significant and complex roles during tumorigenesis and natural aging process. However, the molecular determinants distinguishing senescence from other temporary and permanent cell-cycle arrest states such as quiescence and post-mitotic state and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. In our studies, we aimed to employ multi-omics approaches to deepen our understanding of cellular senescence, in particular, regarding the specific molecular determinants distinguishing cellular senescence from other non-dividing cell fates. Notably, one of the most prominent features of cellular senescence differing from other non-dividing cell fates is the increased expression of senescence-associated beta-galactosidase. Because 5-Dodecanoylaminofluorescein Di-β-D-Galactopyranoside (C12FDG) is known as the substrate catalyzed by ...
Cisplatin Mimics ARF Tumor Suppressor Regulation of RelA (p65) Nuclear Factor-B Transactivation
Antibodies. All antibodies have been described previously ( 15, 17), except the new goat anti-RelA phospho-T505 antibody. This antibody used the same peptide immunogen as described previously ( 17) and was raised by Pacific Immunology Corp ...
Staedtler Lumocolor ink: alternatives to UV-cured ink, alternatives to HP latex ink, alternatives to solvent ink and VOCs
Staedtler Lumocolor, an innovative alternative to UV-cured ink, alternatives to HP latex ink, alternatives to eco-solvent ink: why do these inks (Lumocolor, Kiian from Manoukian, and Magic Ink not get past niche market acceptance? What advantages does Sepiax inks have that may allow them to be significantly more successful?
Natural wax-containing ink jet inks - Patent # 4390369 - PatentGenius
A natural wax-containing ink jet ink for use in an ink jet apparatus which features good print quality. The ink jet ink is discharged from the ink jet ink apparatus at elevated temperatures above ambient.
Mice, Transgenic | Profiles RNS
Pencik J, Schlederer M, Gruber W, Unger C, Walker SM, Chalaris A, Marié IJ, Hassler MR, Javaheri T, Aksoy O, Blayney JK, Prutsch N, Skucha A, Herac M, Krämer OH, Mazal P, Grebien F, Egger G, Poli V, Mikulits W, Eferl R, Esterbauer H, Kennedy R, Fend F, Scharpf M, Braun M, Perner S, Levy DE, Malcolm T, Turner SD, Haitel A, Susani M, Moazzami A, Rose-John S, Aberger F, Merkel O, Moriggl R, Culig Z, Dolznig H, Kenner L. STAT3 regulated ARF expression suppresses prostate cancer metastasis. Nat Commun. 2015 Jul 22; 6:7736 ...
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Stories, Ideas and Perspectives | 300+ Inspirational talks by remarkable people from INK events
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White Ink found in: Higgins Pigment-Based Drawing Ink, Higgins Super White Pigment-Based Waterproof Drawing Ink, Handy Art Block Ink, Jacquard Screen..
Cellular Senescence </b> <...
Cellular senescence is the point at which our cells stop dividing and growing due to damage or lack of necessary components. As cells age, they lose their ability to actively divide and start to undergo senescence.
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الگو:PBB/1029 - ویکیپدیا، دانشنامهٔ آزاد
CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; TP16 ...
OriGene - CDKN2AIPNL (NM 080656) cDNA Clone
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Human CDKN2A/p16INK4a peptide (ab105631) References | Abcam
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Forging a signature of in vivo senescence - Semantic Scholar
Cellular senescence, a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. Proposed relationships between cellular senescence, tumour suppression, loss of tissue regenerative capacity and ageing suffer from lack of uniform definition and consistently applied criteria. Here, we highlight caveats in interpreting the importance of suboptimal senescence-associated biomarkers, expressed either alone or in combination. We advocate that more-specific descriptors be substituted for the now broadly applied umbrella term senescence in defining the suite of diverse physiological responses to cellular stress.
Seasons | Teen Ink
Summer is so sweet Winter is always so cold What does fall feel like? (ok teen ink said I had to enter an article at least a hundred characters long so i'm typing this to make it longer)
Senescence Senescence refers to the biological processes of a living organism approaching an advanced age (i.e., the combination of processes of deterioration
Flintlockjaw: Captain Absolute - inks!
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Teen Ink | Eqrider
I am serious and silly, confident and clumsy, up-in-the-clouds and down-to-earth. I believe in the power of one person, that everyone has made a difference, that every person can love and is loved, and that God lives in everyone.
Toyo Ink CF10464 / #7768ae 헥스 색상 코드 스킴, 챠트, 팔레트, 페인트&RGB / CMYK / HSL 변환
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A cis-element within the ARF locus mediates repression of p16INK4A expression via long-range chromatin interactions | PNAS
Loss of function of CDKN2A/B, also known as INK4/ARF [encoding p16INK4A, p15INK4B, and p14ARF (mouse p19Arf)], confers susceptibility to cancers, whereas its up-regulation during organismal aging provokes cellular senescence and tissue degenerative disorders. To better understand the transcriptional regulation of p16INK4A, a CRISPR screen targeting open, noncoding chromatin regions adjacent to p16INK4A was performed in a human p16INK4A-P2A-mCherry reporter cell line. We identified a repressive element located in the 3′ region adjacent to the ARF promoter that controls p16INK4A expression via long-distance chromatin interactions. Coinfection of lentiviral dCas9-KRAB with selected single-guide RNAs against the repressive element abrogated the ARF/p16INK4A chromatin contacts, thus reactivating p16INK4A expression. Genetic CRISPR screening identified candidate transcription factors inhibiting p16INK4A regulation, including ZNF217, which was confirmed to bind the ARF/p16INK4A interaction loop. In ...
James Robinson Ph.D.
7. G. L. Robinson, J. P Robinson, K. J Lastwika, S.L Holmen and M. W. VanBrocklin. Akt signaling accelerates tumor recurrence following Ras inhibition in the context of Ink4a/Arf loss. 2013 Genes & Cancer, 476-85.. 8. M. W. VanBrocklin, J. P Robinson and S. L Holmen. Ink4a/Arf loss promotes tumor recurrence following Ras inhibition. Neuro-Oncology. 2012 14(1):34-42.. 9. J. P Robinson, M. W. VanBrocklin, K. J Lastwika, A.J. McKinney, S. Brandner and S.L. Holmen. Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo. Oncogene. 2011 30, 1341-. 10. J. P Robinson, M. W. VanBrocklin, A. J McKinney, H.G Gach, and S.L. Holmen. (Akt signaling is required for glioblastoma maintenance in vivo. American Journal of Cancer Research. 2011 1(2):155-167. 11. C. Lai*, J. P Robinson*, S. Clark, G. Stamp, R. Poulsom and A. Silver. Expression Array Profiling Identifies Elevation of WNT5A Expression in Polyp Formation in Lkb1+/- Mice and Peutz-Jeghers Syndrome. The Journal of ...
Latest p16(Ink4a) senescence-reversing research - an important but not game-changing contribution - AGINGSCIENCES™ - Anti-Aging...
Background on cell senescence and P16(Ink4a). P16(Ink4a) has long been known to be associated with cell senescence and aging. In an early draft of my treatise, ANTI-AGING FIREWALLS - THE SCIENCE AND TECHNOLOGY OF LONGEVITY, some three years ago I wrote There appear to be several other clocks related to aging in addition to telomere length. One is the accumulation of INK4a/P16 as well as NF-kappaB in cells with age. And this directly relates to decline in stem cell differentiation as a function of age ? -Buildup of levels of Ink4a/P16 associated with aging slows down the rate of differentiation of adult stem cells. Recent evidence shows that loss of Bmi-1, a polycomb transcriptional repressor of theInk4a-Arf locus, results in progressive loss of HSCs in adult mice with subsequent failure of hematopoiesis. - These results show that either both p16Ink4a and p19Arf can inhibit HSC self-renewal in a serial transplant setting, or that only p16Ink4a is necessary(ref). - A new line of ...
Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression | Development
When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...
ASMscience | New Pathway for p53-Independent Apoptosis
Given that the tumor suppressor ARF stabilizes and activates p53, ARF inactivation has been commonly viewed as one of the many means of inactivating the p53 pathway, a sine qua non for mammalian tumorigenesis. Now Steven R. Grossman and coworkers at the University of Massachusetts Medical School, Worcester, show that ARF causes degradation of a transcription factor, (CtBP) that is a master repressor of pro-apoptotic genes.
Genome-Wide Identification, Phylogeny, and Expression Analysis of ARF Genes Involved in Vegetative Organs Development in...
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Brevet US4638337 - Thermal ink jet printhead - Google Brevets
An improved thermal ink jet printhead is disclosed for ejecting and propelling ink droplets on demand along a flight path toward a recording medium spaced therefrom in response to receipt of electrical input signals representing digitized data signals. Each printhead has one or more capillary filled ink channels. The channels have a droplet emitting nozzle on one end and connect to an ink supplying manifold on the other end. Each channel has a heating element upstream from the nozzle that is located in a recess. The heating elements are selectively addressable with a current pulse for substantially instantaneous vaporization of the ink contacting the addressed heating element to produce a bubble that expels a droplet of ink during its growth and collapse. The recess walls containing the heating elements prevent the lateral movement of the bubbles through the nozzle and therefore the sudden release of vaporized ink to the atmosphere, known as blowout which causes ingestion of air and interrupts the
CDKN2B Gene - GeneCards | CDN2B Protein | CDN2B Antibody
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
CDKN2B Gene - GeneCards | CDN2B Protein | CDN2B Antibody
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
Patent US5563643 - Ink jet printhead and ink supply manifold assembly having ink passageway ... - Google Patents
In a printhead assembly, an ink jet printhead is fixed to the wall of an ink supply manifold. The printhead has an ink inlet in communication with a plurality of nozzles, and the manifold contains liquid ink which flows to the printhead inlet through an outlet in the manifold wall. A preformed hot melt adhesive member with a slot therein is positioned between the manifold wall and the printhead with the slot of the adhesive member surrounding the manifold outlet and printhead inlet, so that when the adhesive member is heated and cooled a hermetic seal is formed.
Patent US5805180 - Ink jet recording apparatus which performs suction recovery with a cap and ... - Google Patents
An ink jet recording apparatus comprising a recording head having discharge ports for discharging the ink, an ink tank for storing said ink to be supplied to the recording head, and suction recovery means for stabilizing the ink discharge from the recording head, characterized in that the suction recovery means has a plurality of suction operations, which can be selected in accordance with the content of the discharge stabilization.
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The function of the squids ink sac is to keep it protected from predators.The ink sac squirts out bursts of ink that allow the squid ample time to escape the...
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What is Alcohol Ink? (with picture)
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It became clear after Letterpress Test 5 and Letterpress Test 6 that this wooden type has a slight spotty texture to it, which was no fault of the inks. The spotty texture was prevalent in both experiments, although the opacity of the black ink when applied liberally managed to hide the texture. If there was not enough ink it quickly became noticeable as the spots would re-emerge ...
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"CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". U.S. National Library of Medicine. Soura E, ... 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 ...
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 ...
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 ... p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ...
"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. ...
"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 ...
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". ...
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 ... 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. ... 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 ...
"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 ...
P16, P-16, or P.16 may refer to: p16, also known as p16Ink4A and CDKN2A, a cyclin-dependent kinase inhibitor involved in tumor ... a United States Army Air Corps biplane developed in the 1920s FFA P-16, a prototype Swiss fighter aircraft developed in the ... suppression AMC Schneider P 16, a French halftrack developed in the 1920s Berliner-Joyce P-16, ...
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 ...
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 ...
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. ...
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. ...
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-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 ... CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... See also CDK inhibitor for inhibitors of various CDKs. Interactions. Cyclin-dependent kinase 4 has been shown to interact ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ...
CDKN2C - ويكيبيديا
"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. ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". مؤرشف من الأصل في 05 ديسمبر 2010.. الوسيط , ...
الگو:PBB/1029 - ویکیپدیا، دانشنامهٔ آزاد
cyclin-dependent protein kinase inhibitor activity. • protein binding. • transcription factor binding. • protein kinase binding ... CDKN2A; ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; ... negative regulation of cyclin-dependent protein kinase activity. • negative regulation of transcription, DNA-dependent. • ... transcription, DNA-dependent. • rRNA processing. • negative regulation of protein kinase activity. • induction of apoptosis. • ...
Cyclin-dependent kinase 8
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 ...
... 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 Rb to pRb, ... One such example of E2F-regulated genes repressed by Rb 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 ...
... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase inhibitor 1A. External IDs. OMIM: 116899 MGI: 104556 HomoloGene: ... CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19). *cip/kip (p21, p27, p57) ... 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 ...
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 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 ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... 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 ... The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... 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. • ...
細胞週期 - 维基百科，自由的百科全书
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
... 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 ... cyclin E and cyclin A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule ... One such example of E2F-regulated genes repressed by Rb are cyclin E and cyclin A. Both of these cyclins are able to bind to ...
ಅಪೊಪ್ಟೋಸಿಸ್ - ವಿಕಿಪೀಡಿಯ
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... cAMP-dependent pathway. *Ca2+ signaling. *Lipid signaling. ... "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic ...
CDK-activating kinase. CDK inhibitor. *INK4a/ARF (p14arf/p16, p15, p18, p19) ... April 2010). "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Res ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... Using these inhibitors it was discovered that cells can die ... The characterization of the caspases allowed the development of caspase inhibitors, which can be used to determine whether a ...
... *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 ...
Kostniakomięsak, wolna encyklopedia
The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... Stwierdzono także mutacje genów supresorowych p16 (CDKN2A), p14 (ARF) i p15 (CDKN2B) wpływających na inaktywację CDK. ... 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 ...
receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor binding. • ubiquitin binding. ... Inhibitors of the MDM2-p53 interaction include the cis-imidazoline analog nutlin. ... Honda R, Yasuda H (March 2000). "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger ... Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE (January 2003). "Cyclin G1 has growth inhibitory ...
Cdk2, la enciclopedia libre
de 1993). «The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases». Cell (UNITED STATES) 75 ... Santamariña, Marta (2008). Efectos de la eliminación de p16 en células tumorales Rb negativas. Univ Santiago de Compostela. p. ... 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. ...
CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) Archived 2004-11-17 at the Wayback Machine from ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) - which has been localised to the p21 region of ... BRAF inhibitors, such as vemurafenib and dabrafenib and a MEK inhibitor trametinib are the most effective, approved treatments ...
Expression of Myc is highly dependent on BRD4 function in some cancers. BET inhibitors have been used to successfully ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also ... Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Letters. 353 (3): 281 ...
"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 ...
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 cyclinsE/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/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 ...
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 ...
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 ...
Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts | PNAS
MAP kinase, cyclin D1, the cyclin-dependent inhibitors, p21 and p16. The percentage of the population actively undergoing DNA ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. David A ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts ... Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts ...
Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with...
Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 (CDKN2) or p16 gene, has been shown to ... Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with ... Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with ... Loss of Expression of the p16/Cyclin-dependent Kinase Inhibitor 2 Tumor Suppressor Gene in Melanocytic Lesions Correlates with ...
Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in...
Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ... Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in ...
Forced expression of the cyclin-dependent kinase inhibitor p16(INK4A) in leukemic U-937 cells reveals dissociation between cell...
Forced expression of the cyclin-dependent kinase inhibitor p16(INK4A) in leukemic U-937 cells reveals dissociation between cell ... MATERIALS AND METHODS: U-937 clones constantly overexpressing the cyclin-dependent kinase inhibitor p16(INK4A) were established ... MATERIALS AND METHODS: U-937 clones constantly overexpressing the cyclin-dependent kinase inhibitor p16(INK4A) were established ... MATERIALS AND METHODS: U-937 clones constantly overexpressing the cyclin-dependent kinase inhibitor p16(INK4A) were established ...
p16-INK4a (Cyclin-dependent kinase inhibitor 2A, Cyclin-dependent kinase 4 inhibitor A, CDK4I, p16INK4A, p16-INK4, Multiple...
p16-INK4a (Cyclin-dependent kinase inhibitor 2A, Cyclin-dependent kinase 4 inhibitor A, CDK4I, p16INK4A, p16-INK4, Multiple ... Cyclin-dependent kinase inhibitor 2A, Cyclin-dependent kinase 4 inhibitor A, CDK4I, p16INK4A, p16-INK4, Multiple tumor ... You are here: Home Products by Molecule of Interest p16-INK4a ( ...
Antibody Database - Conjugates for the antigen 'p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 1)'
... cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 1) in the Antibody Database ... Fluorochrome conjugates for (p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 1)) in the Chromocyte ... p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a (isoform 1) Antibodies by Conjugate. ...
Antibody Database - Reagents for the antigen 'p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a / p19ARF / p14ARF'...
... cyclin-dependent kinase inhibitor 2A / p16INK4a / p19ARF / p14ARF stained with Alkaline Phosphatase (AP) in the Antibody ... p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a / p19ARF / p14ARF Alkaline Phosphatase (AP) Antibodies. ... Antibodies in the Chromocyte database for p16 / CDKN2A / cyclin-dependent kinase inhibitor 2A / p16INK4a / p19ARF / p14ARF and ...
The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the...
... 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 have been shown to be growth suppressors, and the absence or decreased expression of p16 ...
CDKN2A (cyclin dependent kinase 2a / p16)
... p16), Authors: Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire. Published in: Atlas Genet Cytogenet Oncol Haematol. ... cyclin-dependent protein serine/threonine kinase inhibitor activity cyclin-dependent protein serine/threonine kinase inhibitor ... P16-INK4a interacts strongly with cyclin-dependent kinase 4 and cyclin-dependent kinase 6 and inhibits their ability to ... cyclin-dependent protein serine/threonine kinase inhibitor activity cyclin-dependent protein serine/threonine kinase inhibitor ...
April 2013 - Volume 32 - Issue 4 : Cornea
Cyclin-dependent kinase inhibitor protein - Wikipedia
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. ...
Melanoma - Wikipedia
"CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". U.S. National Library of Medicine. Soura E, ... 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 ...
Simultaneous Inactivation of the p16, p15 and p14 Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor...
Based on the sequence data, primers specific for p16, p15 and p14 were designed. Using these primers, the expression of p16, ... Two of the six canine lymphoid tumor cell lines did not express detectable levels of p16, p15 and p14 mRNAs, and wide-ranging ... In this study, the full-length complementary DNA (cDNA) of the canine p16 gene was cloned using the 5 and 3 rapid ... Deletion of the p15-p14-p16 genomic locus could be one of the molecular aberrations in canine lymphoid tumor cells. ...
The Roles of Thyroid and Thyroid Hormone in Pancreas: Physiology and Pathology
... p16Ink4a: cyclin-dependent kinase inhibitor 2; PTF1a: pancreas transcription factor 1a; TR: thyroid hormone receptor; TRIP12: ... The enhanced cyclin D1/cyclin-dependent kinase/retinoblastoma protein/E2F pathway was found to be involved in the process. This ... Also, p16Ink4a (a β cell senescence marker and effector) mRNA expression was increased in rodent and human β cells after T3 ... The effect of T3-dependent cell growth inhibition was demonstrated by fluorescent-activated cell sorting analysis and by cell ...
Uterine smooth muscle tumors of uncertain malignant potential (STUMP): a clinicopathologic analysis of 16 cases
Cyclin-Dependent Kinase Inhibitor p16 * Receptors, Estrogen * Receptors, Progesterone * Tumor Suppressor Protein p53 ... Immunohistochemical stains for p16, p53, MIB1 (ki-67), and estrogen and progesterone receptors were performed. The results were ... Notably, the 2 recurrent tumors were the only ones that were strongly immunoreactive for p16 and p53, supporting earlier ... Both tumors had areas that were indistinguishable from benign leiomyoma and both had diffuse immunoreactivity for p16 and p53. ...
RCSB PDB - Protein Feature View - Cyclin-dependent kinase inhibitor 2A - P42771 (CDN2A HUMAN)
Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16
... in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by ... The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on hu … ... D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the ... Cyclin-Dependent Kinase 4 * Cyclin-Dependent Kinase 6 * Cyclin-Dependent Kinase Inhibitor p16 ...
Centrosome misorientation reduces stem cell division during ageing | Nature
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. . Nature 443, 421-426 (2006) ... p16INK4a induces an age-dependent decline in islet regenerative potential. . Nature 443, 453-457 (2006) ... Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. . Nature 443, 448-452 (2006) ...
Sporadic CDKN2 ( MTS1/p16 ink4 ) gene alterations in human ovarian tumours | British Journal of Cancer
The CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and encompasses three exons. To establish the ... The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D- ... Effect of tumor suppressor gene cyclin-dependent kinase inhibitor 2A wild-type and A148T mutant on the cell cycle of human ... The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D- ...
Patent US8017749 - Compositions and methods to treat cancer with cupredoxins and CpG rich DNA - Google Patents
... a cyclin-dependent kinase inhibitor, such as p16, p21 or p27; a suicide protein such as thymidine kinase or nitroreductase; a ... Aminothiazole inhibitors of cyclin dependent kinases. WO1999027890A2. Nov 30, 1998. Jun 10, 1999. Bristol-Myers Squibb Company ... cyclin dependent kinase inhibitors as found in WO 99/24416 (see also U.S. Pat. No. 6,040,321); and prenyl-protein transferase ... cyclin dependent kinase inhibitors as found in WO 99/24416 (see also U.S. Pat. No. 6,040,321); and prenyl-protein transferase ...
Pharmacological action - C | GreenMedInfo | Natural Medicine
Voltage-Activated K+ Channels and Membrane Depolarization Regulate Accumulation of the Cyclin-Dependent Kinase Inhibitors...
... lacking the cyclin-dependent kinase inhibitors p16INK4a and p19ARF. Our results demonstrate that blockage of K+ channels and ... cyclins and cyclin-dependent kinase inhibitors (cdkis) known to regulate cell cycle progression through this phase are affected ... 1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J ... Blockage of K+ channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27Kip1 ...
Inhibition of melanoma development in the Nras((Q61K)) ::Ink4a(-/-) mouse model by the small molecule BI-69A11.
Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix...
Cyclin-Dependent Kinase Inhibitor p16 / analysis. Cyclin-Dependent Kinase Inhibitor p21 / analysis. Cyclin-Dependent Kinase ... 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Intracellular Signaling Peptides and ... Proteins; 0/Steroids; 0/Tumor Suppressor Protein p53; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27 ... In conclusion, MME induces G1 phase cell cycle arrest via both p53-dependent and p53-independent pathways.. ...
MEDLINE - Resultado p gina 1
0 (Cyclin-Dependent Kinase Inhibitor p16); 0 (DNA, Viral); 0 (Oncogene Proteins, Viral). ... Inibidor p16 de Quinase Dependente de Ciclina/gen tica. Metila o de DNA/gen tica. DNA Viral/gen tica. Epig nese Gen tica/gen ... CONCLUSION: Prognosis of NPC is mainly dependent on histologic type. Prognostic impact of LMP-1 is still unclear since LMP-1 ... The transforming stage is seen as the actual carcinogenic event and can be immunohistochemically detected by the biomarker p16( ...
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cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4). * CMM2. * CDKN2. * CDK4I ... p16(INK4a) (p16) is tight-binding and inhibitory protein for cyclin-dependent kinase 4. Kobayashi S, Shirasawa H, Sashiyama H, ... Regulators of the G1 checkpoint include an inhibitor of cyclin-dependent kinase, p16INK4. Okamoto A, Demetrick DJ, Spillare EA ... Mutation of cell cycle regulators, such as inhibitor of CDK4 or p16 tumor suppressor gene, is a new molecular event in pancreas ...
Differential Effects of the Cyclin-Dependent Kinase Inhibitors p27Kip1, p21Cip1, and p16Ink4 on Vascular Smooth Muscle Cell...
Differential Effects of the Cyclin-Dependent Kinase Inhibitors p27Kip1, p21Cip1, and p16Ink4 on Vascular Smooth Muscle Cell ... predominantly cyclin D-cdk4/6 and cyclin E-cdk2.2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene ... Differential Effects of the Cyclin-Dependent Kinase Inhibitors p27Kip1, p21Cip1, and p16Ink4 on Vascular Smooth Muscle Cell ... Differential Effects of the Cyclin-Dependent Kinase Inhibitors p27Kip1, p21Cip1, and p16Ink4 on Vascular Smooth Muscle Cell ...
Neuronal Cell Death Is Preceded by Cell Cycle Events at All Stages of Alzheimer's Disease | Journal of Neuroscience
1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimers disease. NeuroReport 7:3047-3049. ... 1998) Neuronal expression of cyclin dependent kinase inhibitors of the INK4 family in Alzheimers disease. J Neural Transm 105: ... 1997) G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J ... 1998) Cyclin-dependent kinases participate in death of neurons evoked by DNA-damaging agents. J Cell Biol 143:457-467. ...
Anti-CDKN2A/p16INK4a antibody (ab189302) | Abcam
Cyclin dependent kinase 4 inhibitor A antibody. *Cyclin dependent kinase inhibitor 2A (melanoma p16 inhibits CDK4) antibody ... Cyclin dependent kinase inhibitor 2A isoforms 1/2/3 antibody. *Cyclin dependent kinase inhibitor p16 antibody ... Cyclin dependent kinase inhibitor 2A isoform 4 antibody. * ... Cell Biology Cell Cycle Kinases/Phosphatases Other Share by ... Agonists, activators, antagonists and inhibitors. Lysates. Multiplex Assays. By research area. Cancer. Cardiovascular. Cell ...
Euphorbia tirucalli modulates gene expression in larynx squamous cell carcinoma | BMC Complementary and Alternative Medicine |...
p16: cyclin-dependent kinase inhibitor 2A. P450: cytochrome P450. pb: base pairs ... Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. J Biol Chem. 2006;281(6):3731-7.View ArticlePubMedGoogle ... The genes evaluated in this study showed differential expression in Hep-2 cells in a manner dependent on E. tirucalli latex ... Other project showed that IP3 receptors act as in vivo substrates for Akt kinase, which plays a key role in suppressing ...
INK4aCDKN2AP16INK4AProliferating cell nuExpression of p16INK4CDKN2ProteinsCDK4 and CDK6P16INK4CDKsGeneProtein kinasesInactivationInhibitionCDK6Potent cyclin-dependent kinaseRetinoblastomaMTS1TumorsInhibitoryInhibitsGenesMelanomaAssayProgressionImmunohistochemistryProliferationComplexesPalbociclibArrestRegulatorSmall moleculeKip1CDK2Tumor suppressor proteinActivation of cyclinMutationsFunctions as a tumor suppressorEnzymeSenescent cellsMolecularClasses of CDK inhibitorsImmunohistochemicalLoss of p16Serine-threonDeletionsDevelopment of CDK inhibitorsCellularSenescence
- The p21 family currently includes two related proteins, p27 Kip1 and p57 Kip2 , and the p16 family currently includes four related proteins: p16 INK4a (also variously known as MTS1, CDK4I and CDKN2), p15 INK4b (also known as MTS2), p18 INK4c , and p19 INK4d (reviewed in ref. 10 ). (pnas.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)
- OBJECTIVE: The aim of this study was to investigate how the tumor suppressor protein p16(INK4A) interferes with growth and differentiation of leukemic U-937 cells. (lu.se)
- MATERIALS AND METHODS: U-937 clones constantly overexpressing the cyclin-dependent kinase inhibitor p16(INK4A) were established. (lu.se)
- The effects of high-level expression of p16(INK4A) on proliferation and cell cycle progression were investigated (cell cycle distribution, proliferation rate, analyses of different cell cycle regulatory proteins). (lu.se)
- The effect of introduction of p16(INK4A) on capacity for induced differentiation, assayed by capacity to reduce nitroblue tetrazolium, was determined. (lu.se)
- RESULTS: Overexpressed p16(INK4A) protein was active as judged by its ability to bind to CDK-4 in a coimmunoprecipitation assay. (lu.se)
- Clones overexpressing p16(INK4A) grew slower than controls, without any apparent effects on the phosphorylation status of the retinoblastoma protein (pRb). (lu.se)
- Instead, p16(INK4A) overexpression affected the phosphorylation status of pRb-related pocket protein p130, which was detected in its growth-restraining hypophosphorylated form. (lu.se)
- Despite an enhanced tendency to accumulate in G(0)/G(1), p16(INK4A)-overexpressing cells were less sensitive to induction of differentiation with vitamin D(3) or ATRA than control cells. (lu.se)
- CONCLUSIONS: Constitutive expression of p16(INK4A) in U-937 cells resulted in decreased proliferation as a result of activated p130 rather than pRb. (lu.se)
- Also, we showed that introduction of p16(INK4A) into U-937 cells impaired their capacity to differentiate. (lu.se)
- P16-INK4a interacts strongly with cyclin-dependent kinase 4 and cyclin-dependent kinase 6 and inhibits their ability to interact with cyclins D. P16-INK4a induces cell cycle arrest at G1 and G2/M checkpoints, blocking them from phosphorylating RB1 and preventing exit from G1 phase of the cell cycle. (atlasgeneticsoncology.org)
- P16-INK4a could act as a negative regulator of normal cells proliferation. (atlasgeneticsoncology.org)
- Germline mutations in the p16-INK4a gene were found in approximately 40% of the FAMMM syndrome. (atlasgeneticsoncology.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)
- The transforming stage is seen as the actual carcinogenic event and can be immunohistochemically detected by the biomarker p16(INK4a). (bireme.br)
- p16(INK4a) (p16) is tight-binding and inhibitory protein for cyclin-dependent kinase 4. (bioinformatics.org)
- Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. (bioinformatics.org)
- One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16 INK4a , interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. (clontech.com)
- Thus, p16-INK4a functions as a tumor suppressor in a variety of cells. (clontech.com)
- p16 INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. (clontech.com)
- This product is an affinity-purified IgG antibody that recognizes human p16-INK4a protein. (clontech.com)
- The antibody was raised in mouse using recombinant p16-INK4a and can be used for Western blot (WB) detection, immunohistochemical (IHC) detection, or immunoprecipitation (IP) of human p16-INK4a protein. (clontech.com)
- 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)
- 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)
- 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)
- Here we show that inactivation of the D-type cyclin-dependent kinase inhibitor p16 INK4A is associated with escape from the M0 proliferation block. (asm.org)
- p16 INK4A , originally identified as a protein associating with CDK4 in transformed cells ( 57 ), was cloned in a two-hybrid screen for proteins interacting with CDK4 ( 48 ). (asm.org)
- p16(Ink4a) and p19(Arf): terrible twins . (humpath.com)
- The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16 INK4a and the p53 regulator p14 ARF . (mdpi.com)
- The majority of CDKN2A alterations in melanoma selectively target p16 INK4a or affect the coding sequence of both p16 INK4a and p14 ARF . (mdpi.com)
- There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14 ARF , while not altering the syntenic p16 INK4a coding regions. (mdpi.com)
- We aimed to evaluate the correlation between p16 ink4a -overexpression and high risk (hr)HPV-DNA in vulvar squamous cell carcinoma (vSCC) tumors as well as the impact of both biomarkers on the prognosis of vSCC patients. (biomedcentral.com)
- PCR-detection of (hr)HPV-DNA and immunohistochemical staining for p16 ink4a were conducted in 85 vSCC tumors. (biomedcentral.com)
- p16 ink4a -overexpression and (hr)HPV-DNA were detected in 35 and 37 of the 85 tumors, respectively. (biomedcentral.com)
- P16 ink4a -overexpression, but not (hr)HPV-DNA positivity of the primary tumor, was correlated with prolonged overall survival (OS) ( p = 0.009). (biomedcentral.com)
- Multivariate analysis has demonstrated that lymph node metastasis (HR 1-2.74, 95 % CI 1.50-5.02, p = 0.019), tumor grade (HR 1-2.80, 95 % CI 1.33-5.90, p = 0.007) and p16 ink4a -overexpression (HR 1-2.11, 95 % CI 1.13-3.95, p = 0.001) are independent prognostic factors. (biomedcentral.com)
- The discovered overlap suggests the use of p16 ink4a in combination with HPV-DNA detection as an ancillary test for future research and clinical studies in vSCC. (biomedcentral.com)
- The prognostic and predictive value of p16 ink4a -overexpression should be tested in larger cohort studies. (biomedcentral.com)
- In HPV-transformed cells, the downstream p16 ink4a -CDK4-pRB pathway is blocked by the inactivation of pRB through the HPV E7 protein, and it results in the nuclear and cellular accumulation of the cyclin-dependent kinase inhibitor p16 ink4a [ 2 , 3 ]. (biomedcentral.com)
- The aim of this study was to assess the prevalence of HPV genotypes and the concordance between the presence of (hr)HPV-DNA and p16 ink4a overexpression within vSCC tumors. (biomedcentral.com)
- The secondary aim was to analyze the prognostic significance of p16 ink4a and (hr)HPV-DNA status in vSCC patients. (biomedcentral.com)
- The p16 protein (p16) is an INK4a cyclin-dependent kinase (CDK) inhibitor that decelerates the cell cycle by inactivating the CDK that phosphorylate retinoblastoma (Rb) protein. (cap.org)
- Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 genes. (elsevier.com)
- In addition, fluorescence in situ hybridization (FISH) was performed on EBV-transformed lymphocytes from each affected individual to detect germline copy number of the p16(INK4A)/p14(ARF) tumor suppressor region. (elsevier.com)
- A p53 germline point mutation was identified in one family with some findings of Li-Fraumeni syndrome, and a hemizygous germline deletion of the p16(INK4A)/p14(ARF) tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. (elsevier.com)
- Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases. (elsevier.com)
- CDKN2A (cyclin dependent kinase 2a / p16) Hybridization with Vysis CDKN2A/CEP 9 FISH Probe (Abbott Molecular, US) showing the CDKN2A gene on 9p21.3 (red signals) - Courtesy Adriana Zamecnikova. (atlasgeneticsoncology.org)
- The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. (clontech.com)
- Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. (edu.au)
- P16, also known as CDKN2A, is the symbol for Cyclin-Dependent Kinase Inhibitor 2A. (biocompare.com)
- Overexpression of CDKN2A / p16 in cervical intraepithelial lesions and invasive squamous cell carcinomas (SCCs) associated with high-risk HPV types. (humpath.com)
- Aims To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations. (bmj.com)
- Method Dual-colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. (bmj.com)
- Results Cut-off values for p16/CDKN2A deletion were calculated based on FISH signalling patterns obtained from the benign controls (mean percent nuclei plus three standard deviations). (bmj.com)
- 15% of nuclei showing the monosomy (one p16/CDKN2A , one CEP-9 signal) deletion patterns. (bmj.com)
- None of the benign cases showed a homozygous deletion pattern (no p16/CDKN2A , at least one CEP-9 signal). (bmj.com)
- P16/CDKN2A deletion was detected in 61% (33/54) of MPM cases. (bmj.com)
- Among the equivocal biopsies, four showed homozygous and one showed hemizygous p16/CDKN2A deletion. (bmj.com)
- Age over 60 years, asbestos exposure and p16/CDKN2A deletion were associated with a worse prognosis. (bmj.com)
- FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM. (bmj.com)
- Objectives Because post-transcriptional mechanisms modulate levels of p16 (encoded by CDKN2A ) and p15 (encoded by CDKN2B ), we tested whether interferon-γ regulates the expression of these proteins and the effect of the 9p21 genotype. (onlinejacc.org)
- The common genetic variant located in the vicinity of the genes encoding the cyclin-dependent kinase inhibitors p15 ( CDKN2B ) and p16/ARF ( CDKN2A ) on the short arm of chromosome 9 at 9p21.3 contributes to the risk of CAD by an unknown mechanism that is independent of known risk factors ( 1-3 ). (onlinejacc.org)
- In chordoma cell lines and patient biopsies, the p16 (CDKN2A) tumor suppressor is consistently deleted. (clinicaltrials.gov)
Proliferating cell nu1
- Immunocytochemistry for three cell cycle-related proteins, proliferating cell nuclear antigen, cyclin D, and cyclin B, was performed on sections from hippocampus, basal nucleus of Meynert, and entorhinal cortex. (jneurosci.org)
Expression of p168
- To address the issues of what is the potential involvement of the CDKN2 gene in sporadic melanoma and precisely when during the clinically evident stages of melanoma progression defects in CDKN2 occur, we have evaluated by immunohistochemistry the expression of p16 protein in 103 melanocytic lesions representing all stages in the progression of melanoma. (aacrjournals.org)
- and ( b ) potentially more related to invasiveness or the ability to metastasize, because 52% of primary invasive tumors and 72% of metastatic lesions show partial or complete loss of expression of p16. (aacrjournals.org)
- Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth. (biomedcentral.com)
- Expression of p16 increases markedly with aging in many human tissues. (atlasgeneticsoncology.org)
- Using these primers, the expression of p16, p15 and p14 mRNAs could be individually evaluated by reverse transcriptase polymerase chain reaction. (ceek.jp)
- 30 patients with recurrent ovarian epithelial carcinoma demonstrating Rb-proficiency and absent or low expression of p16 will be registered to receive PD0332991 once a day by mouth in the morning on an empty stomach. (clinicaltrials.gov)
- The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. (nih.gov)
- Results In all cells tested-except HUVECs where expression was not modulated by interferon-γ-regardless of 9p21.3 genotype, interferon-γ increased the expression of p16 and p15. (onlinejacc.org)
- p16 was the first member of the INK4 family characterized and was isolated based upon its interaction with and inhibition of CDK4 ( 11 ). (pnas.org)
- E1-alpha, which is spliced into the common exons E2 and E3, gives rise to the p16-INK4 transcript. (atlasgeneticsoncology.org)
- A putative DNA replication origin has been identified in close proximity of INK4/Arf locus that appears to transcriptionally repress p16 in a manner dependent on CDC6 . (atlasgeneticsoncology.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)
- p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
- 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)
- 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)
- 5 p16 Ink4 is not expressed in normal or injured arteries, but deletions or mutations of p16 Ink4 have been described in human malignancies. (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)
- 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)
- 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)
- In addition, two groups of inhibitors, known as Cip/Kip and INK4 proteins, also regulate cdk activity. (aacrjournals.org)
- Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 ( CDKN2 ) or p16 gene, has been shown to be deleted, mutated, or rear-ranged in a high percentage of sporadic melanoma cell lines, as well as mutated in the germline of a proportion of familial melanoma patients. (aacrjournals.org)
- CDKN2 encodes a M r 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G 1 phase of the cell cycle. (aacrjournals.org)
- Belongs to the cdkn2 cyclin-dependent kinase inhibitor family. (atlasgeneticsoncology.org)
- The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on human chromosome 9p21 (refs 12-14). (nih.gov)
- The frequent deletion or mutation of CDKN2 in tumour cells suggests that p16 acts as a tumour suppressor. (nih.gov)
- The CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and encompasses three exons. (nature.com)
- Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors. (pnas.org)
- Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
- Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. (wikipedia.org)
- The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D-CDK4 complexes. (nature.com)
- 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. (abnova.com)
- PKC (Protein Kinase-C) is a cyclic nucleotide-independent enzyme that phosphorylates serine and threonine residues in many target proteins. (qiagen.com)
CDK4 and CDK69
- To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs. (pnas.org)
- In senescent HDFs, p16 was shown to be complexed to both CDK4 and CDK6. (pnas.org)
- Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases. (pnas.org)
- Three cyclin-dependent kinases, CDK2, CDK4, and CDK6, are involved in the phosphorylation of the Rb protein (reviewed in ref. 5 ). (pnas.org)
- The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (biomedcentral.com)
- Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
- p16 is an inhibitor of the cyclin D-dependent protein kinases CDK4 and CDK6 ( 20 , 48 ), whose main function appears to be the phosphorylation of Rb ( 35 ). (asm.org)
- NSCLCs frequently overexpress cyclin D1 (4 , 5 , 6 , 7) , leading to increased activity of cdk4 and cdk6 and loss of growth control. (aacrjournals.org)
- Cyclin-dependent kinase inhibitor 2A interacts strongly with cdk4 and cdk6. (abbkine.com)
- p16INK4 gene encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4). (humpath.com)
- Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation . (humpath.com)
- The activating cyclins for these CDKs, cyclins D1 and E, are present in senescent cells at similar or elevated levels relative to early passage cells ( 8 ). (pnas.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)
- See also CDK inhibitor for inhibitors of various CDKs. (wikipedia.org)
- Thus in some cancers, notably breast cancer, disregulation of cyclins D and E may result in inappropriate inactivation of Rb due to increased phosphorylation by cyclin-dependent kinases (CDKs) ( 8 , 30 , 61 ). (asm.org)
- Cyclin-dependent kinases (Cdks) comprise a promising set of such targets. (aacrjournals.org)
- Cdks are activated in part by their association with cyclins. (aacrjournals.org)
- 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)
- However, due to the high degree of structural homology within the CDK protein family, putative small-molecule CDK inhibitors may exert their effects through combinatorial inhibition of multiple CDKs and other closely related serine/threonine kinases. (aacrjournals.org)
- Subsequently, p16 was identified as the MTS1 gene representing the melanoma susceptibility locus ( 12 ). (pnas.org)
- Homozygous deletion of p16 gene expression in mice produces normal offspring but shows an increased incidence of lymphomas and sarcomas ( 13 ) unlike similarly p21 expression-deleted mice, which show no increased risk for tumor formation ( 14 ) although mice similarly deleted for p27 Kip1 expression have multiorgan hyperplasias ( 15 , 16 , 17 ). (pnas.org)
- Promoter methylation appears as the commonest mechanism of p16 gene inactivation. (atlasgeneticsoncology.org)
- In this study, the full-length complementary DNA (cDNA) of the canine p16 gene was cloned using the 5' and 3' rapid amplification of cDNA ends methods. (ceek.jp)
- 2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
- Although p16 levels are reduced in a variety of malignancies, this gene product has been shown to be up-regulated and overexpressed in most high-grade cervical dysplasias and carcinomas induced by high-risk HPV subtypes ( 18 ). (aacrjournals.org)
- Hypermethylation in the 5′ p15 gene region was detected in 15 of 23 patients (65%), whereas the 5′ p16 region was unmethylated in all patients. (bloodjournal.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)
- 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. (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. (abnova.com)
- CDK2 and CDK1 are two closely related kinases that play overlapping roles during cell division, contributing to the phosphorylation and inactivation of the retinoblastoma (Rb) tumor suppressor gene product throughout late G 1 , S, and G 2 -M phases ( 5 - 7 ). (aacrjournals.org)
- p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. (wiley.com)
- There was a complete overlap of individual LC 50 values of p16 gene homozygously deleted and p16 germ-line cases for most of the nine classes of drugs tested. (wiley.com)
- Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (curehunter.com)
- Rb inactivation leads to expression of E2F-dependent genes such as thymidine kinase, DNA polymerase-α, cdc2, and cyclin A ( 5 ), which are not expressed in senescent cells ( 6 ), indicating that the failure to phosphorylate Rb is important in the growth arrest of senescent cells. (pnas.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)
- In contrast, reduction of p16 expression did not occur in E7-expressing HMEC that bypassed M0, due to inactivation of Rb. (asm.org)
- These observations in the E6-expressing HMEC correlate well with the finding that CpG island methylation is a mechanism of p16 inactivation in the development of human tumors, including breast cancer. (asm.org)
- The status of Rb expression strongly affects p16 expression, and p16 overexpression has been demonstrated in cervical cancers because of functional inactivation of Rb by HPV E7 oncoprotein. (cap.org)
- most importantly, these inhibitory effects were enhanced by the combination of palbociclib with BYL719 (specific inhibitor of the p110α PI3K-subunit), which promoted a stronger inhibition of GLUT-1 glucose transporter expression, glucose uptake and consumption in comparison with individual treatments, under both normoxic and hypoxic conditions. (springer.com)
- Similarly, inhibition of CDK9 and the subsequent suppression of MCL1 transcription are proposed as a potential mechanism-of-action for the pan-CDK inhibitor flavopiridol in chronic lymphocytic leukemia ( 14 , 15 ). (aacrjournals.org)
- Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. (nih.gov)
- Fascaplysin will therefore prove to be a useful tool in studying the consequence of Cdk4 inhibition, especially in cells containing inactivated p16. (nih.gov)
- 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)
- D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). (nih.gov)
- Predominant p16 complexes contained CDK6 . (rcsb.org)
Potent cyclin-dependent kinase1
- Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. (aacrjournals.org)
- This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. (rcsb.org)
-  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)
- Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells. (nih.gov)
- The p16 cyclin-dependent kinase inhibitor represses the phosphorylation of the retinoblastoma protein (Rb), thereby generating its active, hypophosphorylated form. (springer.com)
- Overall, 91.7% of the specimens demonstrated inactivating alterations in p16/MTS1. (bioinformatics.org)
- p16 up-regulation is a key event in the terminal stages of growth arrest in senescence, which may explain why p16 but not p21 is commonly mutated in immortal cells and human tumors. (pnas.org)
- Both tumors had areas that were indistinguishable from benign leiomyoma and both had diffuse immunoreactivity for p16 and p53. (nih.gov)
- Notably, the 2 recurrent tumors were the only ones that were strongly immunoreactive for p16 and p53, supporting earlier observations that these markers may be helpful in the prediction of the behavior of STUMPs. (nih.gov)
- Unlike in solid tumors, the 5′ region of p15 but not p16 is frequently methylated in AML 5 7 and MDS. (bloodjournal.org)
- Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has been documented in a wide range of solid tumors, including epithelial carcinomas, but causal linkage has only been established in breast carcinoma. (aacrjournals.org)
- Like Rb itself, p16 is a tumor suppressor, as evidenced by its mutation in certain melanoma-prone families and its somatic deletion or mutation in a large percentage of tumors ( 6 , 29 , 43-45 , 50 ). (asm.org)
- Recently, CpG island methylation within the p16 promoter has been identified as a mechanism to eliminate p16 expression in a variety of human tumors ( 23 , 25 , 38 , 44 , 56 ). (asm.org)
- Expression of p21 Waf1/Cip1 , transcriptionally regulated by a p53-dependent pathway (10) , is often decreased in tumors such as NSCLC that harbor p53 mutations. (aacrjournals.org)
- Thus, in cells lacking Rb function, overexpression of p16 is not inhibitory ( 32 , 36 , 37 ). (asm.org)
- A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). (wikipedia.org)
- the interaction inhibits cyclin D- CDK4 kinase activity. (rcsb.org)
- We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. (nih.gov)
- Molecular modelling based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. (nih.gov)
- Use at an assay dependent concentration. (abcam.com)
- We examined p15 and p16 methylation status in bone marrow mononuclear cells from patients with high-risk MDS during treatment with decitabine, using a methylation-sensitive primer extension assay (Ms-SNuPE) to quantitate methylation, and denaturing gradient gel electrophoresis (DGGE) and bisulfite-DNA sequencing to distinguish individually methylated alleles. (bloodjournal.org)
- RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. (nih.gov)
- Immunofluorescence: assay dependent. (genetex.com)
- Western blot: assay dependent. (genetex.com)
- Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. (wikipedia.org)
- Thus, loss of p16, overexpression of D-cyclins and loss of RB have similar effects on G1 progression, and may represent a common pathway to tumorigenesis. (nih.gov)
- 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)
- 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)
- p15 , a target of transforming growth factor-β signaling, 16 is an inhibitor of the cyclin-dependent kinase-4 17 18 and a negative regulator of the G 1 /S progression within the cell cycle. (bloodjournal.org)
- It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
- PKA (Protein Kinase-A) is a second messenger-dependent enzyme that has been implicated in a wide range of cellular processes, including transcription, metabolism, cell cycle progression and. (qiagen.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)
- 2. Baseline paraffin embedded tissue from the patient's primary diagnosis is requested before study enrolment and should be forwarded to the designated central laboratory where central assessment of Rb and p16 expression will be performed by using immunohistochemistry. (clinicaltrials.gov)
- The p16 protein is usually overexpressed in HPV-OPSCC, and its detection on immunohistochemistry is a reliable surrogate marker for this disease. (cancernetwork.com)
- 7 Recommendations from the Lower Anogenital Squamous Terminology (LAST) Project, a collaboration between the College of American Pathologists and the ASCCP, state that Ki-67 should not be routinely added to p16 immunohistochemistry but may be considered in cases for which p16 staining is inconclusive or technically inadequate. (cap.org)
- 8 The role of p16 and Ki67 immunohistochemistry in evaluation of cervical dysplasia is important for both pathologists and clinicians to understand. (cap.org)
- Our findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that β-catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer. (pubmedcentralcanada.ca)
- p19ARF counters uncontrolled proliferation and oncogenic signals in p53 dependent pathways. (novusbio.com)
- This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. (ahajournals.org)
- Thus, these authors suggested that inability to up-regulate p15 and p16 would promote cellular proliferation and atherosclerosis. (onlinejacc.org)
- Thus, chordomas are an example of a tumor with universal activation of the cyclin-dependent kinases 4 and 6 (CDK4/6) pathway, and experiments with patient-derived chordoma cell lines demonstrate aberrant CDK4/6 activity downstream of p16 loss can be efficiently inhibited by the CDK4/6 inhibitor palbociclib, resulting in reduced proliferation and growth of neoplastic cells. (clinicaltrials.gov)
- 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)
- 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)
- 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)
- 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)
- Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
- The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
- 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)
- Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
- Cyclin/CDK complexes were typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mmol/L Tris-HCl (pH 8.0), 10 mmol/L MgCl 2 , 1 mmol/L DTT, and 0.1 mmol/L sodium orthovanadate. (aacrjournals.org)
- Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which coordinate the G1-S transition. (springer.com)
- Here we evaluated the potential of combining palbociclib with PI3K/mTOR inhibitors in Rb-proficient TNBC cells comparing different schedules of treatment: simultaneous, sequential, or sequential combined treatment (pre-incubation with palbociclib followed by exposure to both palbociclib and PI3K/mTOR inhibitors). (springer.com)
- Palbociclib treatment induced AKT signaling, providing a rationale for its combination with PI3K/mTOR inhibitors. (springer.com)
- On the other hand, the sequential combined treatment in which palbociclib was maintained also during exposure to PI3K/mTOR inhibitors gave rise to synergistic anti-proliferative and pro-apoptotic effects, by inhibiting both CDK4/6/Rb/myc and PI3K/mTOR signaling. (springer.com)
- Combination of palbociclib with PI3K/mTOR inhibitors may represent a promising therapeutic option for the treatment of Rb-proficient TNBC, with the sequential combined schedule showing a superior efficacy over the other schedules. (springer.com)
- Recent studies demonstrating clear anticancer efficacy and reduced toxicity of CDK4/6 inhibitors such as palbociclib and multi-CDK inhibitors such as dinaciclib have rejuvenated the field. (aspetjournals.org)
- Favorable results with palbociclib and its recent U.S. Food and Drug Administration approval demonstrate that CDK inhibitors with narrow selectivity profiles can have clinical utility for therapy based on individual tumor genetics. (aspetjournals.org)
- A brief overview of results obtained with ATP-competitive inhibitors such as palbociclib and dinaciclib is presented, followed by a compilation of new avenues that have been pursued toward the development of novel, non-ATP-competitive CDK inhibitors. (aspetjournals.org)
- The investigators aim to conduct a phase II clinical trial to evaluate the efficacy of the small-molecule CDK4/6 inhibitor palbociclib in patients with locally advanced/metastatic chordoma who are not candidates for standard therapy. (clinicaltrials.gov)
- Since p21 decreases after senescence is achieved, this upregulation of p16 may be essential for maintenance of the senescent-cell-cycle arrest. (asm.org)
- Significantly, the ability of p16 to induce cell-cycle arrest is lost in cells lacking functional RB, including primary fibroblasts from Rb-/- mouse embryos. (nih.gov)
- are not involved in ion channel-dependent cell cycle arrest in OP cells. (jneurosci.org)
- The extract markedly up-regulated the expression of p53 and p21WAF1/CIP1 in HepG2, suggesting that MME-induced G1 phase cell cycle arrest in HepG2 might be p53-dependent. (biomedsearch.com)
- In conclusion, MME induces G1 phase cell cycle arrest via both p53-dependent and p53-independent pathways. (biomedsearch.com)
- The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. (nih.gov)
- Treatment of tumour (p16(-), pRb(+)) and normal (p16(+), pRb(+)) cell lines with fascaplysin caused G1 arrest and prevented pRb phosphorylation at sites implicated as being specific for Cdk4 kinase. (nih.gov)
- To define the basis of this phenomenon, we examined the functions of the cyclin dependent kinase (CDK) inhibitors, p16, p21 and p27 in murine GBM astrocytes under conditions that promote Rb-dependent growth arrest. (biomedcentral.com)
- We found that upon serum deprivation or etoposide-induced DNA damage, female, but not male GBM astrocytes, respond with increased p16 and p21 activity, and cell cycle arrest. (biomedcentral.com)
- Based on the intriguing and multifaceted attributes of the CDK target class, several small-molecule CDK inhibitors have entered clinical development ( 19 ). (aacrjournals.org)
- 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)
- Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27 KIP1 ) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. (ahajournals.org)
- TP or HO activity inhibitors decreased p27 KIP1 expression in C2 to the level seen in pC. (ahajournals.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)
- 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)
Tumor suppressor protein1
- The cyclin-dependent kinase inhibitor p16 is a tumor suppressor protein that increases in tissues with age and that is associated with cellular senescence. (medium.com)
Activation of cyclin1
- Conclusions The 9p21.3 risk genotype does not affect the activation of cyclin-dependent kinase inhibitors p15 and p16 by interferon-γ. (onlinejacc.org)
- P16 is functionally inactivated by mutations or deletions, however, because many such mutations occur in exon 2, they can potentially also affect the alternative reading frame (ARF) protein. (atlasgeneticsoncology.org)
- However, point mutations of p16 on the other chromosome are relatively rare. (atlasgeneticsoncology.org)
Functions as a tumor suppressor1
- P16 is a cyclin-dependent kinase inhibitor that regulates the transition from the G 1 to the S phase of the cell cycle and normally functions as a tumor suppressor ( 17 ). (aacrjournals.org)
- cAMP (Cyclic 3, 5-Adenosine Monophosphate)-dependent Protein Kinase, commonly known as PKA (Protein Kinase-A), is a second messenger-dependent enzyme that has been implicated in a wide range of. (qiagen.com)
- A role of the CDK inhibitors in senescence was revealed by the isolation of a cDNA of a highly expressed message in senescent cells that encoded the CDK inhibitor, p21 ( 9 ). (pnas.org)
- Finally, because p16 accumulates in parallel with the increases in senescence-associated β-Gal activity and cell volume that characterize the senescent phenotype, we suggest that p16 upregulation may be part of a differentiation program that is turned on in senescent cells. (asm.org)
- The Mayo Clinic researchers found that they could effectively kill off all of the p16-positive senescent cells in their genetically modified mice by administering a single drug. (medium.com)
- Deletion of the p15-p14-p16 genomic locus could be one of the molecular aberrations in canine lymphoid tumor cells. (ceek.jp)
- This work shows that hyperactivation of the translational machinery is necessary for maintenance of the malignant phenotype in NSCLC, identifies the molecular strategy used to activate translation, and supports the development of lung cancer therapies that directly target the cap-dependent translation initiation complex. (aacrjournals.org)
Classes of CDK inhibitors2
Loss of p161
- Loss of p16 function, like overexpression of cyclins, is predicted to result in higher CDK activity and thus in inappropriate phosphorylation of Rb, effectively inactivating its growth-suppressive effects. (asm.org)
- PKR (Protein Kinase-R) is a 68-kDa serine-threonine kinase that appears to play a primary role in mediating the antiviral activities of infected cells. (qiagen.com)
- Two of the six canine lymphoid tumor cell lines did not express detectable levels of p16, p15 and p14 mRNAs, and wide-ranging deletions in the p15-p14-p16 genomic locus were suspected. (ceek.jp)
- It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. (wiley.com)
- We studied the relationship between p16/p19 ARF deletions, using fluorescence in situ hybridization, and in vitro drug resistance and prognosis in childhood T-ALL at diagnosis. (wiley.com)
Development of CDK inhibitors2
- therefore, this review will emphasize efforts that take new and varied approaches to the development of CDK inhibitors. (aspetjournals.org)
- A critical issue for the successful development of CDK inhibitors (and indeed the majority of cytoreductive agents) is, therefore, the relationship between desirable, target-specific effects and the onset of nonspecific adverse events that might negatively influence clinical dose escalation ( 20 ). (aacrjournals.org)
- During this period, p16 mRNA and cellular protein levels gradually rose with the protein levels in senescent HDFs reaching nearly 40-fold higher than early passage cells. (pnas.org)
- Several lines of evidence have implicated that the Arf/p53/p21, p16/pRB and the DNA-damage response (DDR) pathway regulates cellular senescence [ 6 - 12 ]. (ijbs.com)
- Based upon these results, we propose that senescence is a multistep process requiring the expression of both p21 and p16. (pnas.org)