pRB induces Sp1 activity by relieving inhibition mediated by MDM2

doi:10.1073/pnas.051415898

pRB induces Sp1 activity by relieving inhibition mediated by MDM2

^*Vollum Institute and Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201

Edited by Robert Tjian, University of California, Berkeley, CA, and approved January 2, 2001 (received for review August 30, 2000)

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.

Footnotes

↵ † Present address: Department of Pediatrics, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284.
↵ ‡ To whom reprint requests should be addressed. E-mail: thayerm{at}osu.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

MBP,

maltose-binding protein;

GST,

glutathione S-transferase;

CMV,

cytomegalovirus;

CAT,

chloramphenicol acetyltransferase