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Induction of Transcription by p21Waf1/Cip1/Sdi1: Role of NF?B and Effect of Non-steroidal Anti-inflammatory Drugs
Jason C. Poole, Alison Thain, Neil D. Perkins and Igor B. Roninson
volume 3 | issue 7
july 2004Pages: 931 - 940
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p21Waf1/Cip1/Sdi1 is the primary mediator of cell cycle arrest in response to different forms of stress and in the programs of senescence and differentiation. p21 interacts with many regulatory proteins and has broad effects on cellular gene expression. p21 was previously shown to stimulate NF?B transcriptional activity through its effect on the p300/CBP transcription cofactor family. p21 expression in human cells increases mRNA levels of different genes, some of which have been implicated in carcinogenesis and age-related diseases. Here we report that p21 expression stimulates promoters of six p21-responsive human genes and the cytomegalovirus promoter, as well as an artificial promoter containing NF?B response elements. The I?B? super-repressor blocked the effect of p21 on all but one of the promoters, and the response to p21 was abrogated by the mutagenesis of an NF?B element. p21 inducibility of all the tested promoters and of the endogenous p21-responsive genes was strongly inhibited by adenoviral E1A protein and its deletion mutants that bind p300/CBP but not p21 or Rb. Sulindac and some other non-steroidal anti-inflammatory drugs that inhibit NF?B decrease the effects of p21 on the responsive promoters and endogenous genes. These findings suggest the feasibility of developing agents that
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.