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  • induce
  • Because the p53/p21 axis plays a central role in the DNA damage response and cell cycle control, we directly tested the hypothesis that p21 down-regulation could functionally induce a regenerative response in an appendage of an otherwise nonregenerating mouse strain. (pnas.org)
  • While many are the examples of DNA damaging treatments that induce p21 accumulation, the conception of p21 upregulation as the universal response to genotoxic stress has come to an end. (nih.gov)
  • inhibitor p21
  • Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. (ebi.ac.uk)
  • We further show that the CDK inhibitor p21 begins rising in G2 in mother cells whose daughters exit mitosis into the pre-Restriction Point, CDK2 low state. (pnas.org)
  • proliferating cell nu
  • 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)
  • Białko p21 (WAF1) jest w stanie oddziaływać z jądrowym antygenem komórek proliferujących ( proliferating cell nuclear antigen − PCNA), czynnikiem dodatkowym polimerazy DNA , i tym samym odgrywać rolę regulatora zarówno przy replikacji materiału genetycznego w fazie S jak i przy naprawie łańcucha . (wikipedia.org)
  • regulates
  • Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. (ebi.ac.uk)
  • Here, we determined that p21 regulates macrophage reprogramming by shifting the balance between active p65-p50 and inhibitory p50-p50 NF-κB pathways. (jci.org)
  • inhibition
  • High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. (ebi.ac.uk)
  • While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the consequences of p21/PCNA interaction on cell cycle progression have not yet been determined. (mendeley.com)
  • Our results suggest that p21 might inhibit cell cycle progression by two independent mechanisms, inhibition of cyclin/CDK complexes, and inhibition of PCNA function resulting in both G1 and G2 arrest. (mendeley.com)
  • PCNA
  • p21 binding to PCNA causes G1 and G2 cell. (mendeley.com)
  • Analysis of cells treated with a p21-derived PCNA-binding peptide provides additional evidence that the growth inhibitory effects of p21 and p21CDK result from their ability to bind to PCNA. (mendeley.com)
  • A pre-requisite for CRL4(CDT2)-driven proteolysis is the interaction of p21 with PCNA. (nih.gov)
  • Interestingly as well, CRL4(CDT2)-dependent proteolysis is not limited to p21 and affects other PCNA partners, including the specialized DNA polymerase eta (pol eta). (nih.gov)
  • CDKN1A
  • Using the ear hole closure phenotype, a genetically mapped and reliable quantitative indicator of regeneration in the MRL mouse, we show that the unrelated Cdkn1a tmi/Tyj /J p21 −/− mouse (unlike the B6129SF2/J WT control) closes ear holes similar to MRL mice, providing a firm link between cell cycle checkpoint control and tissue regeneration. (pnas.org)
  • knockdown
  • We found that p21 knockdown with or without cytoplasmic p53 (p53 K305N ) did not significantly influence cell growth in serum-free and 10% FBS-containing media ( Fig. 2 ), suggesting that p21 can regulate cell invasion without significantly altering cell growth. (aacrjournals.org)
  • High p21 levels in sepsis patients correlated with low IFN-β expression, and p21 knockdown in human monocytes corroborated its role in IFN-β regulation. (jci.org)
  • accumulation
  • When this pathway is activated, the final p21 levels are similarly low regardless of the efficient accumulation of a transcriptionally active p53. (nih.gov)
  • complexes
  • 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)
  • p53 and p21 may form complexes with many other proteins. (aacrjournals.org)
  • replication fork stress
  • Moreover, conclusive reports identified the E3-ligase CRL4(CDT2) (CUL4-DDB1-CDT2) as the enzymatic complex that promotes p21 proteolysis when treatments such as UV irradiation trigger replication fork stress. (nih.gov)
  • pathways
  • Diagram depicting the opposite pathways that modulate p21 levels after different types of DNA damage. (nih.gov)
  • The data demonstrate that p21 adjusts the equilibrium between p65-p50 and p50-p50 NF-κB pathways to mediate macrophage plasticity in LPS tolerance. (jci.org)
  • Identifying p21-related pathways involved in monocyte reprogramming may lead to potential targets for sepsis treatment. (jci.org)
  • Localization
  • The binding of the p53/p21 complex to its targets may depend on various factors, including subcellular localization of p53 and p21, cellular physiology, and extracellular stressors. (aacrjournals.org)
  • Chk1
  • Different experimental models (see main text) have shown that ATR activation is required both for the impairment of p21 mRNA transcriptional elongation (with a mechanism that involves CHK1 activation) and for the efficient p21 proteolysis (with a yet unclear mechanism). (nih.gov)
  • CDK4
  • Białko p21 jest silnym inhibitorem kinaz zależnych od cyklin (CKI): wiąże się z kompleksami cyklin CDK2 lub CDK4 , hamując ich aktywność. (wikipedia.org)
  • Białko p21 (WAF1) należy do CKI bezpośrednio hamujących aktywność kompleksów: cyklina E/CDK2 i cyklina D/CDK4. (wikipedia.org)
  • actin
  • p21-ARC is part of a complex implicated in the control of actin polymerization in cells. (abcam.com)
  • ubiquitin
  • 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)
  • Targeting
  • A and B, Empty or p53 K305N -encoding pcDNA3 vectors and control and p21-targeting siRNAs were introduced into H1299 cells in the indicated combinations. (aacrjournals.org)
  • CDK2
  • 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 G 0 /quiescent state, whilst those with low p21 continue to proliferate. (wikipedia.org)
  • regulate
  • Compelling evidences have demonstrated the existence of converging signals that negatively regulate p21 bellow basal levels when replication forks are blocked. (nih.gov)
  • expression
  • Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X-M, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E. Lack of p21 expression links cell cycle control and appendage regeneration in mice . (wikipedia.org)
  • DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. (ebi.ac.uk)
  • The expression of p21 is inducible by a wide range of stress stimuli and its transcription can be enhanced by p53 (6). (genetex.com)
  • Alterations in the levels of p53 or p21 expression did not significantly influence cell growth during similar incubation periods ( 3 ). (aacrjournals.org)
  • Normal cells generally display a rather intense nuclear p21 expression. (biotium.com)
  • Loss of p21 expression has been reported in many carcinomas (gastric carcinoma, non-small cell lung carcinoma, thyroid carcinoma). (biotium.com)
  • Cellular
  • A major finding of our article is that the p53/p21 complex is a functional unit that can act on multiple cellular components and that prosurvival Bcl-2 proteins are targets of the p53/p21 complex. (aacrjournals.org)
  • Human
  • Since ras p21 of Harvey and Kirsten murine sarcoma viruses was identified in 1979 and activated ras oncogenes were found in human tumors in 1982, the growth of ras literature has been a truly impressive phenomenon (Fig. 1). (springer.com)
  • Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases. (mdpi.com)
  • Xiong, X.-D. LincRNA-p21: Implications in Human Diseases. (mdpi.com)
  • synthesis
  • As such, p21 acts as an effective inhibitor of DNA 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)
  • cell cycle
  • 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)
  • regulator
  • p21-ARC is implicated as an important regulator of growth cone translocation, especially in the CNS (Strasser et al, 2004). (abcam.com)
  • activation
  • A) p21 proteolysis is actively induced by UV light in p53+/+ cells (regardless of the efficient, low or undetectable p53 activation) and p53 null cells. (nih.gov)
  • unclear
  • However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. (ebi.ac.uk)
  • affinity
  • p21 deficiency reduced the DNA-binding affinity of the p50-p50 homodimer in LPS-primed and -rechallenged macrophages, impairing their ability to attenuate IFN-β production and acquire an M2-like hyporesponsive status. (jci.org)