Transcriptional activation of the human S100A2 promoter by wild-type p53.
S100A2, a calcium binding protein of the EF-hand family, was recently identified to be inducible by etoposide, a p53 activator. A potential p53 binding site was identified in the promoter of the S100A2 gene, which binds to purified p53 as well as p53 in nuclear extract activated by etoposide. Transactivation assays using the promoter driven luciferase reporters revealed that the S100A2 promoter was transcriptionally activated by wild-type p53, but not by p53 mutants, in a dose-dependent as well as a p53 binding site-dependent manner. The p53-induced transactivation of the S100A2 promoter was enhanced by etoposide and blocked by a dominant negative p53 mutant. Furthermore, endogenous S100A2 mRNA expression is induced by etoposide in p53 positive, but not in p53 negative cells. Thus, p53 appears to positively regulate S100A2 expression.
Tan
M
M
Department of Molecular Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Heizmann
C W
CW
Guan
K
K
Schafer
B W
BW
Sun
Y
Y
D001665:Binding Sites; D002630:Chemotactic Factors / Q000235:genetics*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D009418:S100 Proteins / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002630:Chemotactic Factors; D012333:RNA, Messenger; D009418:S100 Proteins; C098997:S100A2 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide