Brd4-mediated nuclear retention of the papillomavirus E2 protein contributes to its stabilization in host cells.
Brd4-mediated nuclear retention of the papillomavirus E2 protein contributes to its stabilization in host cells.
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Brd4 介导的乳头瘤病毒 E2 蛋白的核保留有助于其在宿主细胞中的稳定
DOI：
10.3390/v6010319
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发表时间：
2014-01-20
期刊：
影响因子：
--
通讯作者：
You J
中科院分区：
文献类型：
--
作者：
Li J;Li Q;Diaz J;You J
乳头瘤病毒E2是一种多功能病毒蛋白，其调节病毒生命周期的许多方面，包括病毒附加体维持、转录激活和抑制。E2通过泛素-蛋白酶体途径降解。细胞布罗莫结构域蛋白Brd 4与E2蛋白的稳定有关。E2通常在细胞质和细胞核之间穿梭。在这项研究中，我们证明E2遍在化主要发生在细胞质中。我们还发现与Brd 4的相互作用促进乳头瘤病毒E2蛋白的核保留，并有助于其在核中的稳定。与野生型E2蛋白相比，核定位缺陷型突变体通过泛素-蛋白酶体途径迅速降解;然而，Brd 4的共表达将这些突变体重定向到细胞核中并显著增加其稳定性。我们进一步证明，将E2蛋白作为双溴结构域融合蛋白或组蛋白2B（H2 B）融合蛋白拴系到染色质显著稳定E2蛋白。我们的研究表明，通过与Brd 4相互作用的E2蛋白的染色质募集防止了E2在细胞质中的泛素化和蛋白酶体降解，导致其在细胞核中的稳定。这些研究为理解Brd 4介导的E2稳定性带来了新的见解，并提供了染色质相关的Brd 4调节E2功能的额外机制。
Papillomavirus E2 is a multifunctional viral protein that regulates many aspects of the viral life cycle including viral episome maintenance, transcriptional activation, and repression. E2 is degraded by the ubiquitin-proteasome pathway. Cellular bromodomain protein Brd4 has been implicated in the stabilization of the E2 protein. E2 normally shuttles between the cytoplasm and the nucleus. In this study, we demonstrate that E2 ubiquitylation mostly occurs in the cytoplasm. We also find that the interaction with Brd4 promotes nuclear retention of papillomavirus E2 proteins and contributes to their stabilization in the nucleus. Compared to wild type E2 proteins, nuclear-localization-defective mutants are rapidly degraded by the ubiquitin-proteasome pathway; however, co-expression of Brd4 redirects these mutants into the nucleus and significantly increases their stability. We further demonstrate that tethering E2 proteins to chromatin as either double-bromodomain fusion proteins or histone 2B (H2B) fusion proteins significantly stabilizes the E2 proteins. Our studies suggest that chromatin recruitment of the E2 protein via interaction with Brd4 prevents E2 ubiquitylation and proteasomal degradation in the cytoplasm, leading to its stabilization in the nucleus. These studies bring new insights for understanding Brd4-mediated E2 stabilization, and provide an additional mechanism by which the chromatin-associated Brd4 regulates E2 functions.
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影响因子：
3.7
作者：
Klueevsek, Kristin;Wertz, Mary;Moroianu, Junona
通讯作者：
Moroianu, Junona
影响因子：
4.8
作者：
Mochizuki, Kazuki;Nishiyama, Akira;Ozato, Keiko
通讯作者：
Ozato, Keiko
DOI：
10.1073/pnas.0407818102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Brannon, AR;Maresca, JA;McBride, AA
通讯作者：
McBride, AA
影响因子：
5.4
作者：
McPhillips, MG;Ozato, K;McBride, AA
通讯作者：
McBride, AA
影响因子：
5.3
作者：
Dey, A;Ellenberg, J;Ozato, K
通讯作者：
Ozato, K