Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein
Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein
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DOI：
10.1073/pnas.94.6.2221
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发表时间：
1997-03-18
影响因子：
11.1
通讯作者：
Flemington, EK
中科院分区：
文献类型：
--
作者：
Campanero, MR;Flemington, EK
E2 F家族转录因子在调控细胞周期进程中起着关键作用，因此，E2 F本身受到一系列转录和转录后事件的严格控制。在此，我们提供证据表明E2 F1蛋白水平受泛素-蛋白酶体依赖的降解途径的调控。对E2 F1突变体的分析鉴定了一个保守的羧基末端区域，该E2 F1羧基末端序列与异源蛋白GAL 4的融合导致GAL 4的去稳定化。以前的研究发现E2 F1的一个重叠区域，促进复合物的形成与视网膜母细胞瘤肿瘤抑制蛋白，pRB，我们发现，pRB块泛素化和稳定E2 F1，这些结果表明一个新的机制，控制细胞周期的调节活性的E2 F1。
The E2F family of transcription factors plays a key role in regulating cell-cycle progression, Accordingly, E2F is itself tightly controlled by a series of transcriptional and posttranscriptional events, Here we provide evidence that E2F1 protein levels are regulated by the ubiquitin-proteasome-dependent degradation pathway, An analysis of E2F1 mutants identified a conserved carboxyl-terminal region, which is required for eliciting ubiquitination and protein turnover, Fusion of this E2F1 carboxyl-terminal sequence to a heterologous protein, GAL4, resulted in destabilization of GAL4. Previous studies identified an overlapping region of E2F1 that facilitates complex formation with retinoblastoma tumor suppressor protein, pRB, and we found that pRB blocks ubiquitination and stabilizes E2F1, These results suggest a new mechanism for controlling the cell-cycle regulatory activity of E2F1.