IndraLab
Statements
"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."