Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600
Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600
复制标题
DOI：
10.1073/pnas.0505337102
复制
发表时间：
2005-08-09
影响因子：
11.1
通讯作者：
Münger, K
中科院分区：
文献类型：
--
作者：
Huh, KW;DeMasi, J;Münger, K
人乳头瘤病毒16型(HPV-16)E7基因编码一种多功能癌蛋白，可颠覆多种细胞调控途径。HPV-16E7癌蛋白最著名的细胞靶点是视网膜母细胞瘤肿瘤抑制蛋白pRb和相关的口袋蛋白p107和p130。然而，有充分的证据表明，E7有更多的细胞靶点，这有助于其转化潜力。我们通过串联亲和纯化和质谱法分离了HPV-16E7相关的细胞蛋白复合体，并确定了600 kDa的视网膜母细胞瘤蛋白相关因子P600是E7的细胞靶点。E7与P600的结合不依赖于Pocket蛋白，是通过N端的E7结构域介导的，该结构域与腺病毒E1a蛋白的保守区1相关，对细胞转化起着不依赖于pRb结合的重要作用。在HPV阳性和阴性的人类癌细胞中，通过RNA干扰耗尽P600蛋白水平大大减少了非锚定生长。因此，P600是E7的一个细胞靶点，它调控有助于锚定非依赖性生长和细胞转化的细胞通路。
The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation.