Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.
It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.
Zambetti
G P
GP
Department of Molecular Biology, Princeton University, New Jersey 08544.
Bargonetti
J
J
Walker
K
K
Prives
C
C
Levine
A J
AJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003402:Creatine Kinase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013696:Temperature; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004247:DNA; D003402:Creatine Kinase