TRANSCRIPTIONAL REPRESSION OF THE E2-CONTAINING PROMOTERS EIIAE, C-MYC, AND RB1 BY THE PRODUCT OF THE RB1 GENE
TRANSCRIPTIONAL REPRESSION OF THE E2-CONTAINING PROMOTERS EIIAE, C-MYC, AND RB1 BY THE PRODUCT OF THE RB1 GENE
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DOI：
10.1128/mcb.12.8.3431
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发表时间：
1992-08-01
影响因子：
5.3
通讯作者：
GALLIE, BL
中科院分区：
文献类型：
--
作者：
HAMEL, PA;GILL, RM;GALLIE, BL
视网膜母细胞瘤易感基因p110RB1的蛋白产物是核磷蛋白[W. H.李，J. Y. Shew，F. D.洪，T. W.塞里湖a.多诺索湖扬河Bookstein和E. y. Lee，Nature（伦敦）329：642 - 645，1987]，具有细胞周期调节剂的性质（K.布赫科维奇湖a. Duffy和E. Harlow，Cell 58：1097 - 1105，1989; P. L.作者：Chen，P. Scully，J. Y. Shew，J. Y。Wang和W. H. Lee，Cell 58：1193 - 1198，1989; J. A.德卡普里奥卢德洛，D. Lynch，Y. Furukawa，J. Griffin，H.皮维尼卡沃尔姆斯角M. Huang和D. M.利文斯顿，细胞58：1085 - 1095，1989;和K. Mihara，X. R. Cao，中国粘蝇A. Yen，S.钱德勒，B。Drivel，A. L. Murphree，A. Tang和Y. K. Fung，Science 246：1300 - 1303，1989）。 尽管p110RB1的作用机制仍不清楚，但一些证据表明它在转录调节中起作用。 我们现在表明，p110RB1的过表达导致腺病毒早期启动子EIIaE和两个细胞基因，c-myc和RB1，这两个基因都含有E2F结合基序的启动子的抑制。 c-myc启动子中E2元件的突变消除了p110RB1的抑制。 我们还表明，p110RB1突变体，这是难治性的细胞周期磷酸化，但完整的E1a/大T抗原结合特性，抑制EIIaE与50 - 80倍的效率比野生型p110RB1。 这些数据提供的证据表明，hypophosphorylated p110 RB1积极抑制基因的表达与启动子含有E2 F结合基序（E2元件）。
The protein product of the retinoblastoma susceptibility gene, p110RB1, is a nuclear phosphoprotein [W. H. Lee, J.Y. Shew, F. D. Hong, T. W. Sery, L. A. Donoso, L. J. Young, R. Bookstein, and E. Y. Lee, Nature (London) 329:642-645, 1987] with properties of a cell cycle regulator (K. Buchkovich, L. A. Duffy, and E. Harlow, Cell 58:1097-1105, 1989; P. L. Chen, P. Scully, J. Y. Shew, J. Y. Wang, and W. H. Lee, Cell 58:1193-1198, 1989; J. A. DeCaprio, J. W. Ludlow, D. Lynch, Y. Furukawa, J. Griffin, H. Piwnica-Worms, C. M. Huang, and D. M. Livingston, Cell 58:1085-1095, 1989; and K. Mihara, X. R. Cao, A. Yen, S. Chandler, B. Driscoll, A. L. Murphree, A. TAng, and Y. K. Fung, Science 246:1300-1303, 1989). Although the mechanism of action of p110RB1 remains unknown, several lines of evidence suggest that it plays a role in the regulation of transcription. We now show that overexpression of p110RB1 causes repression of the adenovirus early promoter EIIaE and the promoters of two cellular genes, c-myc and RB1, both of which contain E2F-binding motifs. Mutation of the E2 element in the c-myc promoter abolishes p110RB1 repression. We also demonstrate that a p110RB1 mutant, which is refractory to cell cycle phosphorylation but intact in E1a/large T antigen-binding properties, represses EIIaE with 50- to 80-fold greater efficiency than wild-type p110RB1. These data provide evidence that hypophosphorylated p110RB1 actively represses expression of genes with promoters containing the E2F-binding motif (E2 element).