Additive effect between NF-kappaB subunits and p53 protein for transcriptional activation of human p53 promoter.
The tumor suppressor p53 plays a pivotal role in the cellular response to DNA damage as it controls DNA repair, cell cycle arrest and apoptosis. We studied the autoregulation of human p53 gene transcription in colon cancer cell lines. Wild-type p53 has been shown to autoregulate its own transcription either positively or negatively and probably in a cell-type-specific manner. Indeed, a p53 binding site has been described in the human and murine p53 promoters, but a direct binding of wild-type p53 protein to this site has never been reported. In this study, we demonstrated a transactivation of human p53 promoter by wild-type p53 in human colon cancer cells. We identified in the human p53 promoter a novel potential p53-responsive element that binds wild-type p53. Moreover, wild-type p53 protein transactivated a reporter plasmid containing a luciferase gene driven by a minimal promoter harboring this p53 binding site. Finally, as the p53 promoter contains an NF-kappaB binding site, we demonstrated an additive effect when NF-kappaB subunits and p53 protein combined to transactivate the human p53 promoter.
Benoit
V
V
Laboratory of Medical Chemistry and Medical Oncology, Pathology B23, University of Liège, Sart-Tilman, Belgium.
Hellin
A C
AC
Huygen
S
S
Gielen
J
J
Bours
V
V
Merville
M P
MP
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics*; D003630:Daunorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005813:Genes, Synthetic; D016158:Genes, p53; D006801:Humans; D008957:Models, Genetic; D016328:NF-kappa B / Q000737:chemistry / Q000502:physiology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D004273:DNA, Neoplasm; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D003630:Daunorubicin