197型人γ-乳头瘤病毒E6和E7相关细胞蛋白的蛋白质组学分析
Proteomic analysis of the gamma human papillomavirus type 197 E6 and E7 associated cellular proteins.
作者信息
Grace Miranda, Munger Karl
机构信息
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, 150 Harrison Avenue, Jaharis 607, Boston, MA, 02111, USA.
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, 150 Harrison Avenue, Jaharis 607, Boston, MA, 02111, USA.
出版信息
Virology. 2017 Jan;500:71-81. doi: 10.1016/j.virol.2016.10.010. Epub 2016 Oct 20.
Abstract
Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing (Arroyo Muhr et al., Int. J. Cancer 136: 2546-55, 2015). To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex. Despite lacking a canonical retinoblastoma (RB1) tumor suppressor binding site, HPV197 E7 binds RB1 and activates E2F transcription. Hence, HPV197 E6 and E7 proteins interact with a similar set of cellular proteins as E6 and E7 proteins encoded by HPVs that have been linked to human carcinogenesis and/or have transforming activities in vitro.
摘要
当通过深度测序分析人类皮肤癌标本时，γ-HPV197是最常鉴定出的人乳头瘤病毒（Arroyo Muhr等人，《国际癌症杂志》136: 2546 - 55，2015年）。为深入了解HPV197的生物学活性，我们研究了HPV197 E6和E7的细胞相互作用组。HPV197 E6蛋白与多种具有LXXLL结构域的细胞蛋白相互作用，包括UBE3A和MAML1。HPV197 E6还能结合并抑制TP53肿瘤抑制因子，并与CCR4-NOT泛素连接酶和去腺苷酸化复合体相互作用。尽管HPV197 E7缺乏典型的视网膜母细胞瘤（RB1）肿瘤抑制因子结合位点，但它能结合RB1并激活E2F转录。因此，HPV197 E6和E7蛋白与已与人致癌作用相关联和/或在体外具有转化活性的HPV所编码的E6和E7蛋白与类似的一组细胞蛋白相互作用。
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