Maf transcriptionally activates the mouse p53 promoter and causes a p53-dependent cell death

An increase in the level of the tumor suppressor protein p53 can induce cel l cycle arrest or cell. death. Although mechanisms for regulating the life span of p53 have been described, there is growing evidence that transcripti onal regulation of the p53 gene contributes significantly to controlling p5 3 protein levels and therefore the fate of a cell. However, the signal tran sduction pathways that lead to transcriptional activation of the p53 gene a re poorly understood. The oncoprotein v-Maf and its cellular counterparts b elong to the large combinatorially complex basic leucine zipper family of t ranscription factors, which include the AP1 family. To date few cellular ta rgets of c-Maf have been identified, It is demonstrated here that v-Maf can bind as a homodimer to a variant Maf recognition element located between - 66 and -54 upstream in the mouse p53 promoter. V-Maf and its cellular count erparts are shown to activate p53 expression through this site. The ability of v-Waf to activate p53 expression is modulated by AP1 family members. In addition, overexpression of v-Maf in primary cells leads to a p53-dependen t cell death. Thus, Maf and members of the AP1 family are able to regulate p53 expression through this site in the p53 promoter.