Regulation of E2F transcription by cyclin E–Cdk2 kinase mediated through p300/CBP co-activators

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作者
Lorna Morris
K. Elizabeth Allen
Nicholas B. La Thangue
机构
[1] University of Glasgow,Division of Biochemistry and Molecular Biology
[2] Rhône-Polenc Rorer Ltd,undefined
来源
Nature Cell Biology | 2000年 / 2卷
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摘要
The E2F proteins form a family of transcription factors that regulate the transition from the G1 to the S phase in the cell cycle. E2F activity is regulated by members of the retinoblastoma protein (pRb) family, ensuring the tight control of E2F-responsive genes. During the G1 phase, phosphorylation of pRb by cyclin-dependent kinases (CDKs), most notably cyclin D–CDK complexes, releases pRb from E2F, facilitating cell-cycle progression by the timely induction of E2F-targeted genes such as cyclin E. However, it is not known whether E2F proteins are directly targeted by CDKs. Here we show that E2F-5 is phosphorylated by the cyclin E–Cdk2 complex, which functions in the late G1 phase, but not by the early-G1-phase-acting cyclin D–CDK complex. A phosphorylation site in the trans-activation domain of E2F-5 stimulates transcription and cell-cycle progression by the recruitment of the p300/CBP family of co-activators, whose binding to E2F-5 is stabilized upon phosphorylation by cyclin E–Cdk2. These results indicate that E2F activity may be directly regulated by cyclin E–Cdk2, and imply an autoregulatory mechanism for cell-cycle-dependent transcription through the CDK-stimulated interaction of E2F with p300/CBP co-activators.
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页码:232 / 239
页数:7
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