Degradation of E2F by the ubiquitin-proteasome pathway: Regulation by retinoblastoma family proteins and adenovirus transforming proteins
Degradation of E2F by the ubiquitin-proteasome pathway: Regulation by retinoblastoma family proteins and adenovirus transforming proteins
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DOI：
10.1101/gad.10.23.2960
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发表时间：
1996-12-01
影响因子：
10.5
通讯作者：
Beijersbergen, RL
中科院分区：
文献类型：
--
作者：
Hateboer, G;Kerkhoven, RM;Beijersbergen, RL
E2 F转录因子是细胞周期中转录的关键调节因子。E2 F活性在转录和DNA结合水平以及通过与视网膜母细胞瘤口袋蛋白家族形成复合物来调节。我们在这里表明，游离E2 F-1和E2 F-4转录因子是不稳定的，它们的降解是由泛素-蛋白酶体途径介导的。E2 F-1和E2 F-4都由于蛋白质羧基末端的表位而变得不稳定，该表位非常接近它们的口袋蛋白相互作用表面。我们发现，E2 F-1与pRb或E2 F-4与p107或p130的结合保护E2 Fs免于降解，使复合物稳定。E2 F-4口袋蛋白复合物的稳定性增加可能有助于维持静止细胞中的活性转录抑制。令人惊讶的是，释放口袋蛋白-E2 F复合物的腺病毒转化蛋白也抑制游离E2 F的分解。这些数据揭示了通过靶向蛋白水解调节E2 F转录因子的额外水平，其被口袋蛋白结合和腺病毒早期区域1转化蛋白抑制。
E2F transcription factors are key regulators of transcription during the cell cycle. E2F activity is regulated at the level of transcription and DNA binding and by complex formation with the retinoblastoma pocket protein family. We show here that free E2F-1 and E2F-4 transcription factors are unstable and that their degradation is mediated by the ubiquitin-proteasome pathway. Both E2F-1 and E2F-4 are rendered unstable by an epitope in the carboxyl terminus of the proteins, in close proximity to their pocket protein interaction surface. We show that binding of E2F-1 to pRb or E2F-4 to p107 or p130 protects E2Fs from degradation, causing the complexes to be stable. The increased stability of E2F-4 pocket protein complexes may contribute to the maintenance of active transcriptional repression in quiescent cells. Surprisingly, adenovirus transforming proteins, which release pocket protein-E2F complexes, also inhibit breakdown of free E2F. These data reveal an additional level of regulation of E2F transcription factors by targeted proteolysis, which is inhibited by pocket protein binding and adenovirus early region 1 transforming proteins.