• 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)
  • Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. (nature.com)
  • Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
  • To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)
  • Aspirin and butyrate effect a growth arrest and an inductction of apoptosis in colorectal cancer cells. (uni-wuerzburg.de)
  • The inhibition of cell proliferation was related to arrest of the cell cycle in the G0/G1 phase and increased apoptosis in response to PTGR1 knockdown as indicated by flow cytometry. (go.jp)
  • High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. (uaeu.ac.ae)
  • Although purvalanol-induced cell cycle arrest and apoptotic cell death were demonstrated in prostate ( 5 ), breast ( 6 ) and colon cancer cells ( 7 ), the exact molecular mechanism of purvanol-induced apoptosis has not been elucidated yet. (spandidos-publications.com)
  • tumor suppressor p53 may induce cell cycle arrest or apoptosis in response to a variety of stress signals such as DNA damage oncogenic stimuli or hypoxia (reviewed in reference 49). (bio2009.org)
  • The fenbendazole-induced apoptosis occurred through the induction of multiple pathways, including p21-mediated cell-cycle arrest. (sunquicksf.com)
  • 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)
  • Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. (conicet.gov.ar)
  • We have shown previously that perifosine induces p21(waf1/cip1) in a p53-independent fashion and that induction of p21(waf1/cip1) is required for the perifosine-induced cell cycle arrest because cell lines lacking p21(waf1/cip1) are refractory to perifosine. (conicet.gov.ar)
  • In this report, we investigated the mechanism by which perifosine induces p21(waf1/cip1) protein expression. (conicet.gov.ar)
  • We observed that perifosine induces the accumulation of p21(waf1/cip1) mRNA without affecting p21(waf1/cip1) mRNA stability. (conicet.gov.ar)
  • Using several p21(waf1/cip1) promoter-driven luciferase reporter plasmids, we observed that perifosine activates the 2.4-kb full-length p21(waf1/cip1) promoter as well as a p21 promoter construct lacking p53-binding sites, suggesting that perifosine activates the p21(waf1/cip1) promoter independent of p53. (conicet.gov.ar)
  • Mutations in each particular Sp1 site block perifosine-induced p21(waf1/cip1) expression. (conicet.gov.ar)
  • Moreover, we showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of Sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased Sp1 binding and enhanced p21(waf1/cip1) transcription. (conicet.gov.ar)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
  • p16, p21, p53, and pRB (phosphorylated retinoblastoma protein) are known as representative protein markers. (dojindo.com)
  • Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. (uaeu.ac.ae)
  • JIB extract induced cell cycle arrest at the G 0 /G 1 phase and decreased cyclin and cdk protein expressions. (medsci.org)
  • ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
  • Western blotting showed that Ets one siRNA resulted in suppression of Ets one protein expression. (checkpointinhibitor.com)
  • Furthermore the p21 protein was shown previously to interact 67346-49-0 with the proliferating cell nuclear antigen (PCNA) thereby preventing DNA replication (10). (bio2009.org)
  • Cellular senescence refers to active cells that eventually enter a state of irreversible growth arrest. (hindawi.com)
  • Studies show that replicative senescence or cellular senescence is induced by intrinsic or extrinsic environmental factors [ 11 ]. (hindawi.com)
  • It was also shown that inhibition of the p16 tumour suppressor gene delays growth arrest and therefore senescence of MSC [ 16 ]. (hindawi.com)
  • Additionally, Abedin and King showed that FGF-2 suppresses the cellular senescence of human MSCs [ 17 ]. (hindawi.com)
  • Relevant cellular senescence markers, such as X-gal staining, cell cycle regulator levels, and the percentage of cell cycle-arrested cells, were found to be reduced in the presence of naringenin. (hindawi.com)
  • Various cellular senescence hallmarks (the percentage of X-gal staining cells, the mRNA levels of the p16 and p21 cell cycle regulators, and the percentage of cell cycle-arrested cells) were investigated. (hindawi.com)
  • Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. (nih.gov)
  • Irreversible cell cycle arrest is one of the phenomena that characterize cellular senescence. (dojindo.com)
  • Doxorubicin (DOX) is known as an anticancer drug that acts in the G2/M phase of the cell cycle to arrest cell proliferation and induce cellular senescence (see the upper left figure). (dojindo.com)
  • Common detection indicators for assessing cellular senescence include features related to cell cycle progression (DNA synthesis, p16/p21 expression, etc.), features related to morphology (of the cell, nucleus, nucleolus, etc. (dojindo.com)
  • p21 has been recognized by virtue of its activation by p53 (13) its association with cyclin/cyclin-dependent kinase (CDK) complexes (23 66 and its up-regulation during senescence (47). (bio2009.org)
  • A: Transfection of p21 siRNA decreased TGF-1 induction of p21 in PTECs, without effect on p27 expression. (holyexperiment.org)
  • Treatment of mouse NIH3T3 cells with 5FU, a potent inhibitor of rRNA maturation, confirmed an activation of this checkpoint, leading to weak induction of the tumor suppressor p53, induction of the Cdk-inhibitor p21, an increase in active, hypo-phosphorylated Rb, and to accumulation of cells in the G1- and S-phase with an increase of cells in G1-phase. (uni-muenchen.de)
  • In contrast, ES cells showed strong induction of p53, but no induction of its target gene p21. (uni-muenchen.de)
  • In this work it could be shown, that butyrate and aspirin in combination enhance the effects on the induction of the cdk inhibitor p21 compared with aspirin and butyrate alone. (uni-wuerzburg.de)
  • Induction of p21 expression by genotoxic stress and its role during terminal differentiation of various cell types have been investigated intensively. (bio2009.org)
  • Recently several reports showed the induction of p21 by inhibitors of histone deacetylases (HDACs) such as for example sodium butyrate (46) trichostatin A (TSA) (56) suberoylanilide hydroxamic acidity (51) oxamflatin (32) MS-27-275 (52) apicidin (22) and trapoxin (54). (bio2009.org)
  • p21 is a potent cyclin-dependent kinase inhibitor (CKI). (wikipedia.org)
  • As such, p21 acts as an effective inhibitor of S-phase DNA synthesis though permits NER, leading to the proposal that p21 acts to preferentially select polymerase processivity factors depending on the context of DNA synthesis. (wikipedia.org)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • 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)
  • Activation of p53 efficiently counteracts deacetylase-mediated repression and induces cell cycle arrest by activating the p21 gene. (bio2009.org)
  • BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. (cancerindex.org)
  • Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance. (babraham.ac.uk)
  • This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. (babraham.ac.uk)
  • According to their nucleolar localization, depletion of Pes1 and Bop1 were shown to inhibit maturation of the 28S rRNA and thereby the large 60S ribosomal subunit. (uni-muenchen.de)
  • In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. (biomedcentral.com)
  • Fenbendazole has also been shown to inhibit the growth of human melanoma, ovarian and prostate cancer cells in vitro. (sunquicksf.com)
  • The tumor suppressor p53 directly interacts with Sp1 and may compete with the transcriptional repressor HDAC1 for binding to the C terminus of Sp1 leading to histone acetylation and concomitant manifestation of p21. (bio2009.org)
  • PTGR1 silencing was found to mechanically enhance the expression of p21, caspase 3, and cleaved PARP and to decrease the level of cyclin D1. (go.jp)
  • 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)
  • CDKs show their action by interacting with cyclins and different CDK-cyclin complexes regulate the cell cycle in the G1, S and G2/M phases ( 1 ). (spandidos-publications.com)
  • The transcriptional activation from CACNA1F the p21 gene by these inhibitors is normally marketed by chromatin redecorating pursuing acetylation of histones H3 and H4 in the p21 promoter area (32 54 This activation of p21 takes place within a p53-unbiased fashion and for that reason HDAC inhibitors are appealing realtors for cancers therapy being that they are operative in cells with mutated p53 genes a hallmark of several tumors. (bio2009.org)
  • In addition to its function as a transcriptional activator Sp1 offers been recently shown to act as a repressor by recruiting HDAC1 to the growth-regulated murine thymidine kinase gene (TK) promoter (11). (bio2009.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • effects the main target for p53-induced cell cycle arrest seems to be the p21 gene. (bio2009.org)
  • Likewise the p21 67346-49-0 gene could be turned on by transforming development aspect β Ca2+ lovastatin or nerve development aspect (16). (bio2009.org)
  • The promoter from the individual p21 gene harbors six conserved GC containers binding sites for the transcription aspect Sp1. (bio2009.org)
  • With this statement we display that HDAC1 is definitely a crucial regulator of p21 gene manifestation. (bio2009.org)
  • 5FU treated ES cells showed an accumulation of cells in S-phase instead. (uni-muenchen.de)
  • Increased sensitivity to genotoxic agents, particularly ultraviolet light and methylmethanesulfonate, shows that Brca2 function is essential for the ability to survive DNA damage. (nih.gov)
  • 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)
  • Arrest in the G1 and G2/M phases is accompanied by elevated p53 and p21 expression. (nih.gov)
  • In addition, it increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in the colonic tissues. (carcinogenesis.com)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • Clinicopathologic analysis showed that Annexin A2 expression was significantly correlated with clinical stage, and lymph node metastasis. (jcancer.org)
  • Mechanistically, our studies showed that knockdown of Annexin A2 increased the expression of p53, which in turn, induced cell cycle G2 arrest and inhibited epithelial-to-mesenchymal transition (EMT). (jcancer.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)
  • Furthermore, Nar has been demonstrated to bind to estrogen receptors [ 5 - 8 ] and shows bidirectional adjusting effects [ 9 ]. (hindawi.com)
  • 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)
  • 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)
  • p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. (wikipedia.org)
  • While p21 is usually activated by p53-dependent mechanisms in response to DNA damage to make sure cell cycle arrest and repair a number of realtors that promote differentiation like phorbol ester 67346-49-0 or okadaic acidity can up-regulate p21 separately of p53 (for an assessment see reference point 16). (bio2009.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)
  • The minimal p21 promoter region required for perifosine-induced p21 promoter activation contains four consensus Sp1-binding sites. (conicet.gov.ar)
  • Luciferase reporter constructs driven by the human being p21 promoter were previously. (bio2009.org)
  • During this work, the function of the proteins Pes1, Bop1 and WDR12, which were shown previously to be involved in ribosome biogenesis of mature cell lines, was investigated in mouse ES cells. (uni-muenchen.de)
  • In addition acetylation of transcription factors offers been shown elsewhere to impact the stability and intracellular localization of proteins or to modulate the affinity for DNA or additional proteins (34). (bio2009.org)
  • Hence, ribosomal stress does not lead to checkpoint activation via the p53-p21-Rb pathway in ES cells. (uni-muenchen.de)
  • Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. (nih.gov)
  • In mature cells, disruptions in ribosome biogenesis are directly linked to the cell cycle machinery by a p53-dependent activation of the G1/S-phase checkpoint, leading to an arrest of cells in G1-phase. (uni-muenchen.de)
  • p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.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)
  • Here we show that multinucleate OIS cells originated mostly from failed mitosis. (nih.gov)
  • The results showed that patients treated with AED had a significantly longer survival than those who were not. (biomedcentral.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)
  • 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)
  • Working in mouse models, it was also shown that whilst mice lacking p21 were healthy, spontaneous tumours developed and G1 checkpoint control was compromised in cells derived from these mice. (wikipedia.org)
  • Impaired ribosome biogenesis is known to activate a p53-dependent checkpoint in mature cell lines, which leads to an arrest of cells in G1-phase. (uni-muenchen.de)
  • Thermal stability assays show that ERKi do not destabilise ERK2 (or ERK1) in vitro, suggesting that ERK2 turnover is a cellular consequence of ERKi binding. (babraham.ac.uk)
  • 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)
  • Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21. (wikipedia.org)
  • Reported figures from the WHO show rates of smoking in Egypt as high as 20% but limited information is available about smoking specifically among physicians and medical students. (who.int)
  • Xpa −/− mice showed a significant elevation in liver tumors. (aacrjournals.org)
  • In this study, we showed that Annexin A2 was evidently overexpressed in human NSCLCs cell lines and NSCLCs tissues. (jcancer.org)
  • p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (wikipedia.org)
  • The median survival of Xpc −/− mice showed a significant decrease, whereas the median survival of Xpa −/− mice did not. (aacrjournals.org)
  • In the last years, extensive investigation on miRNomics have shown to have great advantages in cancer personalized medicine regarding diagnosis, treatment and even clinical outcomes. (frontiersin.org)
  • Bee venom (BV) is an attractive candidate because many experimental and clinical reports show that BV exhibits anti-inflammatory, anti-apoptotic, anti-fibrotic, antibacterial, antiviral, antifungal, and anticancer effects. (blogspot.com)
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
  • mmc9.pdf (66K) GUID:?55F9BD4F-0F85-40B3-99F0-75E20D3D96BC Supplemental Physique?S10 Silencing p21 reversed cell cycle G2/M arrest of TGF-1Ctreated proximal tubular epithelial cells. (holyexperiment.org)
  • The figure on the left shows the results of an experiment in which DOX was added to A549 cells. (dojindo.com)
  • We showed that depending on the concentrations used, Salinomycin elicits different effects on theMDA-MB-231 cells. (uaeu.ac.ae)
  • Collectively, our results indicate that JIB extract showed anti-tumor effects and synergized with cisplatin against B16/F10 cells, indicating the possibility of JIB extract to be developed as adjuvant therapy for melanoma. (medsci.org)
  • ST (30-90 μM) treatments for 48 h and 72 h did not show any significant effect on cell growth and death in A431 cells. (biomedcentral.com)
  • While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. (biomedcentral.com)
  • This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. (biomedcentral.com)
  • While much work has focused on the failure of epithelial cell populations as a key component of the aging process, additional studies have shown that aging, as a global phenomenon in the lung, also impacts resident endothelial, mesenchymal, and immune cell populations. (karger.com)
  • Various studies have shown that asthmatic ASMCs are involved in hyperresponsiveness and the inflammatory and remodelling processes of severe asthma [ 4 ]. (ersjournals.com)
  • Strikingly, Xpa −/− and Xpc −/− mice also showed a phenotypical difference in terms of tumor spectrum. (aacrjournals.org)
  • Despite the similar shape of the benzene molecule and the pyridinium cation, the experimental and simulated data have showed clear differences in their dynamics. (pdgfrsignaling.com)
  • To test the hypothesis that escape from G1 arrest in drug promotes amplification, we exploited the combination of palbociclib and selumetinib. (babraham.ac.uk)