pRB induces Sp1 activity by relieving inhibition mediated by MDM2

被引:43
作者
Johnson-Pais, T
Degnin, C
Thayer, MJ
机构
[1] Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA
[2] Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA
关键词
D O I
10.1073/pnas.051415898
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2211 / 2216
页数:6
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