Regulation of the 26S proteasome by adenovirus E1A.
Regulation of the 26S proteasome by adenovirus E1A.
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腺病毒 E1A 对 26S 蛋白酶体的调节。
DOI：
10.1093/emboj/19.17.4759
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Gallimore,PH
中科院分区：
文献类型：
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作者：
Turnell,AS;Grand,RJ;Gorbea,C;Zhang,X;Wang,W;Mymryk,JS;Gallimore,PH
我们已经确定腺病毒早期区域1A的N末端(AdE1A)是一个调节26S蛋白酶体的区域。具体地说，体外和体内共沉淀研究表明，蛋白酶体的19S调节成分Sug1(S8)和S4通过Ad5 E1a的氨基酸(AA)4-25结合。与不结合蛋白酶体的N末端AdE1A突变体相比，野生型(Wt)AdE1A在体内的表达与模拟感染细胞相比，降低了与抗S4免疫沉淀物相关的ATPase活性。这种ATPase活性的降低与wt AdE1A显著降低HPV16E6靶向泛素介导的蛋白酶体降解的能力的能力呈正相关，而与N端缺失突变体无关。AdE1a/蛋白酶体复合体存在于胞浆和胞核中，提示AdE1a干扰核蛋白酶体和胞质蛋白酶体的降解。我们还证明了wt AdE1a和N端AdE1a缺失突变体是蛋白酶体介导的降解的底物。然而，AdE1A的降解不是通过泛素化介导的，而是通过C-末端PEST区域(AA 224-238)中残基的磷酸化来调节的。
We have identified the N‐terminus of adenovirus early region 1A (AdE1A) as a region that can regulate the 26S proteasome. Specifically, in vitro and in vivo co‐precipitation studies have revealed that the 19S regulatory components of the proteasome, Sug1 (S8) and S4, bind through amino acids (aa) 4–25 of Ad5 E1A. In vivo expression of wild‐type (wt) AdE1A, in contrast to the N‐terminal AdE1A mutant that does not bind the proteasome, reduces ATPase activity associated with anti‐S4 immunoprecipitates relative to mock‐infected cells. This reduction in ATPase activity correlates positively with the ability of wt AdE1A, but not the N‐terminal deletion mutant, to significantly reduce the ability of HPV16 E6 to target p53 for ubiquitin‐mediated proteasomal degradation. AdE1A/proteasomal complexes are present in both the cytoplasm and the nucleus, suggesting that AdE1A interferes with both nuclear and cytoplasmic proteasomal degradation. We have also demonstrated that wt AdE1A and the N‐terminal AdE1A deletion mutant are substrates for proteasomal‐mediated degradation. AdE1A degradation is not, however, mediated through ubiquitylation, but is regulated through phosphorylation of residues within a C‐terminal PEST region (aa 224–238).