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 cell cycle arrest or cell death. Although mechanisms for regulating the life span of p53 have been described, there is growing evidence that transcriptional regulation of the p53 gene contributes significantly to controlling p53 protein levels and therefore the fate of a cell. However, the signal transduction pathways that lead to transcriptional activation of the p53 gene are poorly understood. The oncoprotein v-Maf and its cellular counterparts belong to the large combinatorially complex basic leucine zipper family of transcription factors, which include the AP1 family. To date few cellular targets 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 counterparts are shown to activate p53 expression through this site. The ability of v-Maf to activate p53 expression is modulated by AP1 family members. In addition, overexpression of v-Maf in primary cells leads to a p53-dependent cell death. Thus, Maf and members of the AP1 family are able to regulate p53 expression through this site in the p53 promoter.
Hale
T K
TK
Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin, New Zealand. tracy.hale@stonebow.otago.ac.nz
Myers
C
C
Maitra
R
R
Kolzau
T
T
Nishizawa
M
M
Braithwaite
A W
AW
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D002645:Chickens; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D001426:Bacterial Proteins; C081169:Maf protein, Bacillus subtilis; D016159:Tumor Suppressor Protein p53; D004247:DNA