Degradation of Id proteins by the ubiquitin-proteasome pathway
Degradation of Id proteins by the ubiquitin-proteasome pathway
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DOI：
10.1096/fasebj.13.15.2257
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发表时间：
1999-12-01
期刊：
影响因子：
4.8
通讯作者：
Christy, BA
中科院分区：
文献类型：
--
作者：
Bounpheng, MA;Dimas, JJ;Christy, BA
Id蛋白通过形成转录失活蛋白复合物作为bHLH转录因子的负调节因子。这些蛋白质的功能包括促进细胞生长和细胞周期进程、诱导细胞凋亡和抑制细胞分化。我们研究了泛素介导的蛋白水解途径在Id 3蛋白降解中的作用。我们发现Id 3是一个短寿命的蛋白质，并估计在293细胞中的半衰期类似于20分钟。使用26 S蛋白酶体的特异性抑制剂和在必需的El泛素激活酶中具有温度敏感性缺陷的突变成纤维细胞，我们表明Id 3和相关的Idl和Id 2蛋白通过泛素-蛋白酶体途径降解。我们发现Id 4蛋白对26 S蛋白酶体抑制剂的敏感性要低得多，但其降解依赖于El酶。此外，我们观察到bHLH蛋白E47与Id 3的共表达显著降低了Id 3的降解速率，表明Id 3在与bHLH蛋白复合时对26 S蛋白酶体的降解不太敏感。
Id proteins act as negative regulators of bHLH transcription factors by forming; transcriptionally inactive protein complexes. The proposed function of these proteins includes promotion of cell growth and cell cycle progression, induction of apoptosis, and inhibition of cellular differentiation. We investigated the role of the ubiquitin-mediated proteolytic pathway in the degradation of the Id3 protein. We found Id3 to be a short-lived protein and estimated the half-life to be similar to 20 min in 293 cells, Using specific inhibitors of the 26S proteasome and mutant fibroblast cells with a temperature-sensitive defect in the essential El ubiquitin-activating enzyme, we show that Id3 and the related Idl and Id2 proteins are degraded through the ubiquitin-proteasome pathway. We found the Id4 protein to be much less sensitive to inhibitors of the 26S proteasome, but its degradation was dependent on the El enzyme. In addition, we observed that coexpression of the bHLH protein E47 with Id3 significantly reduced the rate of degradation of Id3, suggesting that Id3 is less susceptible to degradation by the 26S proteasome when complexed to a bHLH protein.