Transcriptional repression by p53 through direct binding to a novel DNA element.

TitleTranscriptional repression by p53 through direct binding to a novel DNA element.
Publication TypeJournal Article
Year of Publication2001
AuthorsJohnson RA, Ince TA, Scotto KW
JournalJ Biol Chem
Date Published2001 Jul 20
KeywordsATP Binding Cassette Transporter, Subfamily B, Member 1, Base Sequence, Binding Sites, DNA, DNA Primers, Humans, Protein Binding, Repressor Proteins, Transcription, Genetic, Tumor Cells, Cultured, Tumor Suppressor Protein p53

The tumor suppressor protein p53 has been well documented as a transcriptional activator involved in the regulation of a number of critical genes involved in the cell cycle, response to DNA damage, and apoptosis. Activation by p53 requires the interaction of the protein with a consensus binding site consisting of two half-sites, each comprising two copies of the sequence PuPuPuC(A/T) arranged head-to-head and separated by 0-13 base pairs. In addition to activation, p53 has been shown to be a potent repressor of transcription. However, the basis for p53-mediated repression is not well understood and has been proposed to occur indirectly through interactions with other promoter-bound transcription factors. In the present study, we show that p53 can repress transcription directly by binding to a novel head-to-tail (HT) site within the MDR1 promoter. A mutation that disrupted p53 binding to the MDR1 HT site blocked p53-mediated repression of the MDR1 promoter in transfection assays. Replacement of the HT site with a head-to-head (HH) site converted the activity of p53 from repression to activation, indicating that simple recruitment of p53 to the promoter is not sufficient for repression and that the orientation of the binding element determines the fate of p53-regulated promoters.

Alternate JournalJ Biol Chem
PubMed ID11350951
Grant ListP01-CA18856-15 / CA / NCI NIH HHS / United States
P30-CA-08748 / CA / NCI NIH HHS / United States
R01-CA57307 / CA / NCI NIH HHS / United States
Related Faculty: 
Tan Ince, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700