pRB induces Sp1 activity by relieving inhibition mediated by MDM2

Teresa Johnson-Pais, Catherine Degnin, Mathew J. Thayer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

pRB activates transcription by a poorly understood mechanism that involves relieving negative regulation of the promoter specificity factor Sp1. We show here that MDM2 inhibits Sp1-mediated transcription, that MDM2 binds directly to Sp1 in vitro as well as in vivo, and that MDM2 inhibits the DNA-binding activity of Sp1. Forced expression of pRB relieves MDM2-mediated repression, and interaction of pRB with the MDM2-Sp1 complex releases Sp1 and restores DNA binding. These results suggest a model in which the opposing activities of MDM2 and pRB regulate Sp1 DNA-binding and transcriptional activity.

Original languageEnglish (US)
Pages (from-to)2211-2216
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number5
DOIs
StatePublished - Feb 27 2001

ASJC Scopus subject areas

  • General

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