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Cell cycle progression is regulated by interactions betweencyclins and cyclin-dependent kinases(CDKs).p21~(WAF1)is oneof the CIP/KIP family which inhibits CDKs activity.Increasedexpression of p21~(WAF1)may play an important role in thegrowth arrest induced in transformed cells.Although thestability of the p2~(WAF1)mRNA could be altered by differentsignals,cell differentiation and numerous influencingfactors.However,recent studies suggest that two knownmechanisms of epigenesis,i.e.gene inactivation bymethylation in promoter region and changes to an inactivechromatin by histone deacetylation,seem to be the bestcandidate mechanisms for inactivation of p21~(WAF1).To date,almost no coding region p21~(WAF1)mutations have been foundin tumor cells,despite extensive screening of hundreds ofvarious tumors.Hypermethylation of the p21~(WAF1)promoterregion may represent an altemative mechanism by which thep21~(WAF1/CIP1)gene can be inactivated.The reduction of cellularDNMT protein levels also induces a corresponding rapidincrease in the cell cycle regulator p21~(WAF1)proteindemonstrating a regulatory link between DNMT and p21~(WAF1)which is independent of methylation of DNA.Both histonehyperacetylation and hypoacetylation appear to be importantin the carcinoma process,and induction of the p21~(WAF1)geneby histone hyperacetylation may be a mechanism by whichdietary fiber prevents carcinogenesis.Here,we review theinfluence of histone acetylation and DNA methylation onp21~(WAF1)transcription,and affection of pathways or factorsassociated such as p53,E2A,Sp1 as wall as several histonedeacetylation inhibitors.
Cell cycle progression is regulated by interactions betweencyclins and cyclin-dependent kinases (CDKs) .p21 ~ (WAF1) is oneof the CIP / KIP family which inhibits CDKs activity .creasedexpression ofp21 ~ (WAF1) may play an important role in thegrowth arrest induced in transformed cells. Although thestability of the p2 ~ (WAF1) mRNA could be altered by differentsignals, cell differentiation and numerous influencing factors. Recent, recent studies suggest that two known mechanisms of epigenesis, iegene inactivation bymethylation in promoter region and changes to an inactivechromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21 ~ (WAF1) .To date, almost no coding region p21 ~ (WAF1) mutations have been found in tumor cells, extensive screening of hundreds ofvarious tumors. Hypermethylation of the p21 ~ (WAF1) promoterregion may represent an altemative mechanism by which thep21 ~ (WAF1 / CIP1) gene can be inactivated. The reduction of cellularDNMT protein levels also induc es a corresponding rapidincrease in the cell cycle regulator p21 ~ (WAF1) proteindemonstrating a regulatory link between DNMT and p21 ~ (WAF1) which is independent of methylation of DNA.Both histonehyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21 ~ (WAF1) geneby histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the effect of histone acetylation and DNA methylation onp21 ~ (WAF1) transcription, and affection of pathways or factors associated with such p53, E2A, Sp1 as wall as several histonedeacetylation inhibitors.