• The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase. (wikipedia.org)
  • identified a protein p21 (WAF1) which was present in cells expressing wild type p53 but not those with mutant p53, moreover constitutive expression of p21 led to cell cycle arrest in a number of cell types. (wikipedia.org)
  • The inhibitory effects of esculetin on cell viability were found to be associated with a G1 arrest in cell cycle progression that was concomitant with an inhibition of cyclin E and an induction of cyclin-dependent kinase (Cdk) inhibitor p21/WAF1/CIP1 in a p53-independent manner. (dsmc.or.kr)
  • In addition, BMP-2 overexpression induced p21 WAF1/CIP1 and p27 KIP1 expression, and cellular apoptosis in RCC cells. (oncotarget.com)
  • Particular emphasis was placed on the roles of growth arrest and c-Myc, p27 Kip1 , and p21 WAF1 expression, because all of these elements contribute to clonal deletion. (aai.org)
  • Finally, in contrast to clonal deletion, PAH-induced pro/pre-B cell death was not dependent on p27 Kip1 or p21 WAF1 up-regulation but did coincide with p53 induction. (aai.org)
  • A second, potentially overlapping pathway, leading to anti-Ig-induced, immature B cell growth arrest and death, involves p53-dependent up-regulation of p21 WAF1 ( 8 ). (aai.org)
  • In particular, our data suggests that the cyclin-dependent kinase inhibitor p21 (Cip1/Waf1), which is expressed in response to DNA damage, promotes quiescence by blocking positive feedback loops that facilitate G1 progression downstream of serum stimulation. (cellcycle.org.uk)
  • The expression of cyclin-dependent kinase inhibitors was profoundly affected with early activation and then repression of p21 cip1/waf1 and persistent activation of both p27 kip1 and p57 kip2 , whereas genes involved in cell survival and proliferation were suppressed. (aacrjournals.org)
  • EBF3 bound directly to p21 cip1/waf1 promoter and regulated transcription from both p21 cip1/waf1 and p27 kip1 promoters in reporter assays. (aacrjournals.org)
  • Protein levels of CDKN1A -encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. (biomedcentral.com)
  • Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. (biomedcentral.com)
  • In view of the importance that the checkpoint G1 / S in the viral replication plays, it is not surprising that HIV-1 proteins, Indeed, as has been shown that the activity t of G1 / S Our own studies, we observed the activity cyclin E/CDK2 kinase complexes, the t in HIV-infected cells of a fa erh ht Is latent because of the loss of natural CDK inhibitor p21/waf1. (micrornalibrary.com)
  • Cdk inhibitor p21/waf1 is normally cellular p53 in Ren induced stress and regulates the G1 / S transition by inhibiting the activity of t of cyclin / cdk complexes. (micrornalibrary.com)
  • Studies from our laboratory have shown that an HIV-infected T-cells of F Latent expression of p21/waf1 is not to breach the host cell They induce. (micrornalibrary.com)
  • The lack of expression of p21/waf1 was on physical and functional interaction of Tat with p53, which then caused due no inactivation of p53. (micrornalibrary.com)
  • The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • The crosstalk is regulated by tumor suppressor proteins, including ARF, P21 and FBXW7, which are also frequently mutated in many cancers. (biomedcentral.com)
  • Various physiological and pathological conditions such as glucose starvation, inhibition of protein glycosylation and oxidative stress may cause an accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to the unfolded protein response (UPR) and autophagy. (spandidos-publications.com)
  • 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. (thermofisher.com)
  • E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. (e3ligasesignal.com)
  • Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, may have functions beyond that of cell cycle regulation. (biomedcentral.com)
  • Survivin belongs to the family of inhibitors of apoptosis proteins (IAPs) that plays a pivotal role in mitotic progression, apoptosis inhibition, angiogenesis, progression of cancer, and invasion [ 5 ]. (springeropen.com)
  • AA and the extracellular regulated protein kinase 1/2 (ERK1/2) blocker U0126 markedly inhibited migration, elevated smooth muscle 22 α (SM22 α ) expression, repressed VSMC proliferation, elevated miR-466f-3p and miR-425-3p expression, and suppressed miR-27a-5p and miR-128-5p expression in ox-LDL-induced VSMCs. (hindawi.com)
  • This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • These effects were associated with inhibition of the mitogen‑activated protein kinase/extracellular signal‑regulated kinase 1/2 and protein kinase B signaling pathways. (spandidos-publications.com)
  • The underlying mechanisms of these effects were primarily mediated by G 1 phase cell cycle arrest and inhibition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulate kinase 1/2 (Erk 1/2) and protein kinase B (Akt) signaling pathways. (spandidos-publications.com)
  • This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. (wikipedia.org)
  • However p21 may inhibit apoptosis and does not induce cell death on its own. (wikipedia.org)
  • The ability of p21 to inhibit apoptosis in response to replication fork stress has also been reported. (wikipedia.org)
  • Moreover, the models also predict that mutations of RAS, ARF and P21 in the context of HMGB1 signaling can influence the cancer cell's fate - apoptosis or survival - through the crosstalk of different pathways. (biomedcentral.com)
  • New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
  • That SP600125 induces endoreduplication signals, promotes tubulin polymerization, a critical process in cell division, and induces delayed apoptosis in leukemia Aurora kinases cells. (hsp90-inhibitors.com)
  • In addition, cell cycle distribution analysis revealed that G0/G1 phase arrest was induced following pristimerin treatment in CAL‑27 and SCC‑25 cells, which was strongly associated with upregulation of p21 and p27, coupled with downregulation of cyclin D1 and cyclin E. Meanwhile, pristimerin induced significant apoptosis of CAL‑27 and SCC‑25 cells, alongside decreased levels of caspase‑3 and specific cleavage of poly (ADP‑ribose) polymerase. (spandidos-publications.com)
  • In addition to apoptosis induction ( 11 ), the mechanisms involved in the anticancer effects of pristimerin include stimulation of reactive oxygen species generation ( 15 ), blocking of nuclear factor-κB ( 16 ) and proteasome inhibition ( 10 ). (spandidos-publications.com)
  • Enhanced apoptosis was correlated with loss of pro-survival factors (XIAP, bcl-2, bcl-xL), expression of pro-apoptotic markers (caspases 3/7, PARP cleavage) and enhanced cell cycle regulators p21 and p27. (biomedcentral.com)
  • Survivin is an apoptosis inhibitor that is associated with tumor proliferation and invasion. (springeropen.com)
  • The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
  • p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2. (wikipedia.org)
  • The binding of p21 to CDK complexes occurs through p21's N-terminal domain, which is homologous to the other CIP/KIP CDK inhibitors p27 and p57. (wikipedia.org)
  • also found that γ-irradiation of fibroblasts induced a p53 and p21 dependent cell cycle arrest, here p21 was found bound to inactive cyclin E/CDK2 complexes. (wikipedia.org)
  • 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)
  • Transforming growth factor-β1 (TGF-β) signals through a serine/threonine-kinase receptor pathway. (janechin.net)
  • Recent work has now found that in human cell lines SCFSkp2 degrades p21 towards the end of G1 phase, allowing cells to exit a quiescent state, whilst CRL4Cdt2 acts to degrade p21 at a much higher rate than SCFSkp2 over the G1/S transition and subsequently maintain low levels of p21 throughout S-phase. (wikipedia.org)
  • This indicates that high levels of p21 and Cdk2 can be expressed at different times in G2 M arrest and endoreduplication because endoreduplication occurs after G2 M arrest. (hsp90-inhibitors.com)
  • It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
  • Therefore, the upregulation of p21 expression may contribute to G2 M arrest in the early stages, and then Cdk2 may regulate endoreduplication by treating leukemia cells in the middle stages in the presence of SP600125. (hsp90-inhibitors.com)
  • Follow up work, found evidence that this bistability is underpinned by double negative feedback between p21 and CDK2, where CDK2 inhibits p21 activity via ubiquitin ligase activity. (wikipedia.org)
  • Farnesyltransferase inhibitor tipifarnib is well leurocristine tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic tumor survival pathways in patients with advanced multiple myeloma. (hsp90-inhibitors.com)
  • Wu M, Sun Y, Xu F, Liang Y, Liu H, Yi Y. Annexin A2 Silencing Inhibits Proliferation and Epithelial-to-mesenchymal Transition through p53-Dependent Pathway in NSCLCs. (jcancer.org)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)
  • Thereafter, L St TFIIH the complex dissociates and the dissociation preinitiation inhibition of CDK9 autophosphorylation, which is for effective binding of T1 to TAR RNA cdk9/cyclin required. (micrornalibrary.com)
  • High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4 Cdt2 and SCF Skp2 couple to degrade p21 prior to the G1/S transition. (cellcycle.org.uk)
  • Some studies have reported that the G2 M arrest induced by SP600125 may be due to inhibition of cyclin B Cdk1 kinase activity through an increase in p21 levels. (hsp90-inhibitors.com)
  • Thus, inhibition of JNK activity prevents dissociation between p21 and JNK, and then prevents inhibition of cyclin B Cdk1 activity, leading to induction of G2 M arrest. (hsp90-inhibitors.com)
  • Therefore, SP600125 has a strong anticancer effect against leukemia cells in a dose and time dependent manner by promoting tubulin polymerization and disrupting the organization of the microtubule cytoskeleton. (hsp90-inhibitors.com)
  • Farnesyltransferase inhibitor as anticancer agent. (hsp90-inhibitors.com)
  • Digalloyl-resveratrol (di-GA) is a synthetic compound aimed to combine the biological effects of the plant polyhydroxy phenols gallic acid and resveratrol, which are both radical scavengers and cyclooxygenase inhibitors exhibiting anticancer activity. (nature.com)
  • Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21. (wikipedia.org)
  • We present experimental evidence that cells gradually lose this ability to revert to quiescence as they progress through G1 and that the onset of rapid p21 degradation at the G1/S transition prevents this response altogether, insulating S-phase from mild, endogenous DNA damage. (cellcycle.org.uk)
  • The migration, phenotypic transformation, and proliferation of VSMCs lead to vascular wall remodeling, which is mediated by activation of extracellular regulated protein kinases 1/2 (ERK1/2) signalling [ 9 ]. (hindawi.com)
  • Here, using live single cell measurements of p21 protein in proliferating cultures, we show that naturally-occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. (cellcycle.org.uk)
  • p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (wikipedia.org)
  • Studies of p53 dependent cell cycle arrest in response to DNA damage identified p21 as the primary mediator of downstream cell cycle arrest. (wikipedia.org)
  • Purvalanol, a novel cyclin-dependent kinase inhibitor, is referred to as a strong apoptotic inducer which causes cell cycle arrest in various cancer cells such as prostate, breast and colon cancer cell lines. (spandidos-publications.com)
  • The present study has shown that an increase in p21 expression coincides with the onset of G2 M arrest at 24 h, but that endoreduplication may occur due to loss of p21 and a maximum level of Cdk2 at 48 h. (hsp90-inhibitors.com)
  • Following DNA damage caused by exogenous sources, such as ionising radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. (cellcycle.org.uk)
  • Knockdown of Annexin A2 significantly suppressed cell proliferation and invasion of NSCLCs cells, and the biological effect of Annexin A2 on proliferation and invasion was mediated by the inhibition of p53, which in turn, promoted cell cycle progression and EMT. (jcancer.org)
  • In the present study, our aim was to determine the time-dependent, ER-mediated apoptotic and autophagy induction of purvalanol in HCT 116 colon cancer cells. (spandidos-publications.com)
  • By the treatment of CDK4 inhibitor, the induction or the maintenance of Long-term potentiation (LTP) in response to a strong tetanus and NMDA receptor-dependent long-term depression (LTD) were normal in hippocampus. (biomedcentral.com)
  • Cytoplasmic p21 expression can be significantly correlated with lymph node metastasis, distant metastases, advanced TNM stage (a classification of cancer staging that stands for: tumor size, describing nearby lymph nodes, and distant metastasis), depth of invasion and OS (overall survival rate). (wikipedia.org)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
  • HMGB1 can activate a series of signaling components, including mitogen-activated protein kinases (MAPKs) and AKT, which play an important role in tumor growth and inflammation, through binding to different surface receptors, such as RAGE and TLR2/4. (biomedcentral.com)
  • BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy. (biomedcentral.com)
  • The 3′UTR-binding sequence site of miR-128-5p on the p21 gene was predicted and assessed by luciferase assays. (hindawi.com)
  • p21 is a potent cyclin-dependent kinase inhibitor (CKI). (wikipedia.org)
  • Increased JNK activity is important for the dissociation of p21 and JNK, following which cells enter into the S phases. (hsp90-inhibitors.com)
  • Experiments looking at CDK2 activity within single cells have also shown p21 to be responsible for a bifurcation in CDK2 activity following mitosis, cells with high p21 enter a G0/quiescent state, whilst those with low p21 continue to proliferate. (wikipedia.org)
  • Recent work exploring p21 activation in response to DNA damage at a single-cell level have demonstrated that pulsatile p53 activity leads to subsequent pulses of p21, and that the strength of p21 activation is cell cycle phase dependent. (wikipedia.org)
  • this responsible for the bifurcation in CDK2 activity observed in Spencer et al. (wikipedia.org)
  • CDK4 may be useful as a prognostic marker for hepatocellular carcinoma and its kinase activity has been reported to promote the progression of T cell acute lymphoblastic leukemia. (rndsystems.com)
  • Cyclin E/CDK2 is the main cyclin / CDK complex, whose maximal activity is t observed in the sp Th G1 / S boundary. (micrornalibrary.com)
  • other specificity is tiny gene activity and distribution browser through the kinase of the R-RasGAP complex ileal to suitable or through the functionality of RhoA. (evakoch.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)
  • Olomoucine, roscovitine and purvalanol are examples of CDK inhibitors (CDKIs) designed and investigated for their apoptotic potential on cancer cells ( 3 ). (spandidos-publications.com)
  • Vitamin D is also known to exert rapid effects that are not dependent on gene transcription [ 5 ]. (biomedcentral.com)
  • inositol-requiring enzyme 1 (IRE1α), PRKR-like ER kinase (PERK) and activating transcription factor-6 (ATF-6). (spandidos-publications.com)
  • Recently, a growing body of evidence that r is given On a different cyclin / CDK complex, n Namely Cyclin E/CDK2 in Tat-activated transcription. (micrornalibrary.com)
  • Two generation myocardiocytes, ERCC5( XPG) and the extracellularspace of ERCC1 and ERCC4( XPF), have associated to the free favour subunit to appear the library planning that will migrate the caspase-dependent gamma from the small opening growth( Dunand-Sauthier et al. (evakoch.com)
  • Signaling specificity is conferred by receptors and mediated through associated-kinases. (janechin.net)
  • However, long-term depression (LTD) induced either by group I metabotropic glutamate receptors (mGluRs) agonist or by paired-pulse low-frequency stimulation (PP-LFS) was impaired in CDK4 inhibitor pretreated slices both from neonatal and adolescent animals. (biomedcentral.com)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • The miR-128-5p mimic promoted the migration and proliferation of VSMCs and suppressed p21, p27, and SM22ɑ expression. (hindawi.com)
  • The inhibitor increased p21, p27, and SM22ɑ expression and repressed the migration, phenotypic transformation, and proliferation of VSMCs. (hindawi.com)
  • miR-128-5p directly targeted the 3′UTR-binding sequences of the p21 gene, negatively regulated p21 expression, and supported the proliferation of VSMCs. (hindawi.com)
  • Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4 kinase activities with no change in their expression. (dsmc.or.kr)
  • Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
  • Nevertheless, additional experiments are necessary to determine why p21 expression is significantly increased due to SP600125 treatment. (hsp90-inhibitors.com)
  • Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). (biomedcentral.com)
  • p21 interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. (wikipedia.org)
  • Specifically, p21 has a high affinity for the PIP-box binding region on PCNA, binding of p21 to this region is proposed to block the binding of processivity factors necessary for PCNA dependent S-phase DNA synthesis, but not PCNA dependent nucleotide excision repair (NER). (wikipedia.org)
  • Studies have also demonstrated that the E3 ubiquitin ligase complex CRL4Cdt2 degrades p21 in a PCNA dependent manner over S-phase, necessary to prevent p21 dependent re-replication, as well as in response to UV irradiation. (wikipedia.org)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • Several studies have shown that miRNAs play multiple roles in the phenotypic transformation, migration, and proliferation of VSMCs by inhibiting ERK1/2 activation [ 11 , 12 ], partly by regulating the tissue inhibitor of metalloproteinases (TIMPs)-MMPs and p21-cyclins interactions [ 13 - 18 ]. (hindawi.com)
  • Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma. (cancerindex.org)
  • CDK4 inhibition decreases homologous recombination and increases non-homologous end joining, suggesting that CDK4 may also promote error free DNA repair. (rndsystems.com)
  • Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
  • SIRT2, an NAD-dependent class III histone deacetylase, contributes to H4-K16Ac deacetylation and DNA compaction in human fibroblast cell lines that assemble striking senescence-associated heterochromatin foci (SAHFs). (biomedcentral.com)
  • Treatment of senescent cells with trichostatin A, a class I/II histone deacetylase inhibitor, also induced rapid and reversible decondensation of SAHFs. (biomedcentral.com)
  • In budding yeast, heterochromatin is formed by the localized action of the Sir2 NAD-dependent histone deacetylase that specifically deacetylates H4-K16Ac to allow binding of the SIR silencing complex [ 8 ]. (biomedcentral.com)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Somatostatin , peptide with 14 amino acids, 3 mg per day, injected slowly in the evening after supper, subcutaneously or intravenously with a 12-hour timed syringe (evening administration is indispensable since this coincides with the nocturnal peak in GH and GH-dependent growth factors). (beatingcancercenter.com)
  • Cyclin E/CDK2 has been shown to play an R Important by regulating the release of factors, including normal Rb E2F sequestered in the transition from G1 / S. (micrornalibrary.com)