Smith E J, Leone G, DeGregori J, Jakoi L, Nevins J R
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Cell Biol. 1996 Dec;16(12):6965-76. doi: 10.1128/MCB.16.12.6965.
Previous studies have demonstrated cell cycle-dependent specificities in the interactions of E2F proteins with Rb family members. We now show that the formation of an E2F-p130 complex is unique to cells in a quiescent, G0 state. The E2F-p130 complex does not reform when cells reenter a proliferative state and cycle through G1. The presence of an E2F-p130 complex in quiescent cells coincides with the E2F-mediated repression of transcription of the E2F1 gene, and we show that the E2F sites in the E2F1 promoter are important as cells enter quiescence but play no apparent role in cycling cells. In addition, the decay of the E2F-p130 complex as cells reenter the cell cycle requires the action of G1 cyclin-dependent kinase activity. We conclude that the accumulation of the E2F-p130 complex in quiescent cells provides a negative control of certain key target genes and defines a functional distinction between these G0 cells and cells that exist transiently in G1.
先前的研究已经证明了E2F蛋白与Rb家族成员相互作用中存在细胞周期依赖性特异性。我们现在表明,E2F-p130复合物的形成是静止的G0期细胞所特有的。当细胞重新进入增殖状态并通过G1期循环时,E2F-p130复合物不会重新形成。静止细胞中E2F-p130复合物的存在与E2F介导的E2F1基因转录抑制相吻合,并且我们表明,当细胞进入静止期时,E2F1启动子中的E2F位点很重要,但在循环细胞中没有明显作用。此外,当细胞重新进入细胞周期时,E2F-p130复合物的降解需要G1期细胞周期蛋白依赖性激酶活性的作用。我们得出结论,静止细胞中E2F-p130复合物的积累对某些关键靶基因提供了负调控,并定义了这些G0期细胞与短暂存在于G1期的细胞之间的功能差异。