pRB induces Sp1 activity by relieving inhibition mediated by MDM2.
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.
Johnson-Pais
T
T
Vollum Institute and Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201, USA.
Degnin
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C
Thayer
M J
MJ
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D051379:Mice; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015032:Zinc / Q000378:metabolism
D017931:DNA Primers; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016329:Sp1 Transcription Factor; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D015032:Zinc