Published online Jun 15, 2002. doi: 10.3748/wjg.v8.i3.400
Revised: December 22, 2001
Accepted: February 7, 2002
Published online: June 15, 2002
Cell cycle progression is regulated by interactions between cyclins and c yclin-dependent kinases (CDKs). p21WAF1 is one of the CIP/KIP family which inhib its CDKs activity. Increased expression of p21WAF1 may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21WAF1 mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21WAF1. To date, almost no coding region p21WAF1 mutations have been found in tumor cells, despi te extensive screening of hundreds of various tumors. Hypermethylation of the p21WAF1 promoter region may represent an alternative mechanism by which the p21WAF1/CIP1 gene can be inactivated. The reduction of cellular DNMT prote in levels also induces a corresponding rapid increase in the cell cycle regulator p21WAF1 protein demonstrating a regulatory link between DNMT and p21WAF1 which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induct ion of the p21WAF1 gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of hi stone acetylation and DNA methylation on p21WAF1 transcription, and affect ion of pathways or factors associated such as p53, E2A, Sp1 as well as sever al histone deacetylation inhibitors.