THE E2F TRANSCRIPTION FACTOR IS A CELLULAR TARGET FOR THE RB PROTEIN
THE E2F TRANSCRIPTION FACTOR IS A CELLULAR TARGET FOR THE RB PROTEIN
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DOI：
10.1016/0092-8674(91)90557-f
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发表时间：
1991-06-14
期刊：
影响因子：
64.5
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
--
作者：
CHELLAPPAN, SP;HIEBERT, S;NEVINS, JR
虽然人们普遍认为视网膜母细胞瘤易感基因（RB 1）的产物是细胞增殖的重要调节因子，但其作用的生化机制尚不清楚。我们现在发现RB蛋白与E2 F转录因子形成复合物，并且只有RB的磷酸化不足形式存在于E2 F复合物中。此外，腺病毒E1 A蛋白可以解离E2 F-RB复合物，依赖于E1 A序列，这对于E1 A与RB结合也是至关重要的。这些序列对于E1 A使原代细胞培养物永生化以及与其他癌基因一起转化也是至关重要的。两者合计，这些结果表明，RB与E2 F的相互作用是控制细胞增殖的重要事件，并且复合物的解离是E1 A使RB功能失活的机制的一部分。
Although it is generally believed that the product of the retinoblastoma susceptibility gene (RB1) is an important regulator of cell proliferation, the biochemical mechanism for its action is unclear. We now show that the RB protein is found in a complex with the E2F transcription factor and that only the underphosphorylated form of RB is in the E2F complex. Moreover, the adenovirus E1A protein can dissociate the E2F-RB complex, dependent on E1A sequence also critical for E1A to bind to RB. These sequences are also critical for E1A to immortalize primary cell cultures and to transform in conjunction with other oncogenes. Taken together, these results suggest that the interaction of RB with E2F is an important event in the control of cellular proliferation and that the dissociation of the complex is part of the mechanism by which E1A inactivates RB function.