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Published on: January 21, 2012
pRB induces Sp1 activity by relieving inhibition mediated by MDM2
T Johnson-Pais1, C Degnin, M J Thayer
1Vollum Institute and Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201, USA.
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.
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