IndraLab
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"Unexpectedly, while Wip1 depletion increased DAXX phosphorylation both before and after DNA damage and increased p53 stability and transcriptional activity, knock-down of DAXX impacted neither p53 stabilization nor p53 mediated expression of Gadd45a, Noxa, Mdm2, p21, Puma, Sesn2, Tigar or Wip1."
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"Our data suggested that combined treatment of the C4-2B cell line with RES and DTX indicates that the up-regulation of p53 expression stimulates the expression of p21 WAF1 and CIP1 and p27 KIP1 and suppresses the expression of cyclin D1 and CDK4 complex thus blocks the progression of cells from G 1 to S phase."
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"AF metabolites, presumably though the CYP and SULT driven bioactivation pathway, have been shown to be DNA damaging agents, inducing DNA protein crosslinks, cytokeratin-RNA crosslinks, phosphorylation of p53, increased expression of p21, gamma-Histone 2AX (gamma-H2AX), reactive oxygen species mediated apoptosis, and S-phase arrest in sensitive populations of cells [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."
TP53 acetylated on K164, K370, K120, K373, K372, K382, K386, and K381 increases the amount of CDKN1A. 7 / 7
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"In this study, we found that a subset of ING family members strongly repressed human alpha-fetoprotein (AFP) promoter activity but stimulated the p21(WAF1) promoter in parallel experiments in the same cell type, similar to the effects of p53. Both ING1 and p53 were able to suppress AFP transcription and cause p21 induction; hSIR2, a negative regulator of the p53 protein, showed the opposite effects on the AFP promoter and, like HDAC1, repressed p21 promoter activity."
"from full text - Box 2 | Bcl2 and the Rb/Arf/p53 network Inactivation of the retinoblastoma (Rb) pathway — for example, by loss of cell-cycle inhibitor Ink4a, which can prevent cyclin-D–Cdk4 from phosphorylating Rb — unleashes the transcription factor E2f1,which increases expression of Arf, a protein that is encoded by the same locus as Ink4a (REF. 136).Arf,which is also a transcriptional target of Myc, sequesters Mdm2, a negative regulator of p53. Raised p53 levels can either impose growth arrest, typically by inducing the Waf1 cell-cycle inhibitor, or promote apoptosis through targets such as Bax, Puma and Noxa. The apoptotic targets seem to also require the p53 relative p63 or p73 (REF. 152). Circles/ovals denote oncogene products; rectangles denote known or likely tumour suppressors. For more detail, see REFS 4–6,136.ATM, ataxia telengiectasia mutated; Chk2, checkpoint 2; NF-?B, nuclear factor-?B."
"The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents."
"The p21 gene is under the transcriptional control of p53 (ref. 5), suggesting that p21 might promote p53-dependent cell cycle arrest or apoptosis. p21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage. p53 then transcriptionally upregulates the expression of target genes, of which p21 is critical for inhibiting g1/s entry."
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"A possible mechanism behind the changes in SWI-SNF composition could be that phosphorylation of TMF-1 by Fer and/or PDGFRbeta promotes disruption of the TMF-1-containing repressive SWI and SNF complex; this may lead to release of Brg-1 followed by its binding to p53, which activates the transcription of CDKN1A, although interaction with the kinase inactive receptor may maintain a repressive SWI and SNF complex and inhibit p21 expression."
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"Dox-induced expression of p53-R273H or p53-L344P mutants failed to increase p21 expression as assessed by RNA-FISH measurements of the percentage of cells with active p21 transcription sites (Figure 4B), by p21 nascent RNA levels (Figure 4C, blue), and by the number of p21 RNA molecules per cell (Figures 4D and S4H)."