Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.
Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.
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DOI：
10.1038/onc.2012.534
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发表时间：
2013-10-17
期刊：
影响因子：
8
通讯作者：
Dutta, A.
中科院分区：
文献类型：
--
作者：
Gupta, A.;Jha, S.;Engel, D. A.;Ornelles, D. A.;Dutta, A.
腺病毒是线性双链DNA病毒，感染人类和啮齿动物细胞系，偶尔转化它们并在动物模型中引起肿瘤。宿主细胞以多方面的方式挑战病毒，以抑制病毒基因表达和DNA复制，有时甚至通过程序性细胞死亡消除受感染的细胞。为了应对这些挑战，腺病毒废除了细胞DNA损伤反应途径。Tip60是一种赖氨酸乙酰转移酶，乙酰化组蛋白和其他蛋白质以调节基因表达、DNA损伤反应、凋亡和细胞周期调节。Tip60是真正的肿瘤抑制因子，因为对于Tip60是单倍体的小鼠易患肿瘤。我们已经发现Tip60通过蛋白酶体介导的途径被腺病毒癌蛋白EIB55K和E4orf6降解。Tip60与立即早期腺病毒启动子结合并抑制腺病毒EIA基因表达，该基因是腺病毒转录的主要调节因子，至少部分通过在该启动子上保留病毒编码的阻遏物pVII。因此，腺病毒早期蛋白降解Tip60对于有效的病毒早期基因转录和细胞基因表达的变化是重要的。
Adenoviruses are linear double stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor since mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.
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影响因子：
16
作者：
Jha S;Vande Pol S;Banerjee NS;Dutta AB;Chow LT;Dutta A
通讯作者：
Dutta A
影响因子：
5.3
作者：
Jha, Sudhakar;Shibata, Etsuko;Dutta, Anindya
通讯作者：
Dutta, Anindya
影响因子：
5.4
作者：
Karen, Kasey A.;Hearing, Patrick
通讯作者：
Hearing, Patrick
影响因子：
5.4
作者：
Nevels, M;Täuber, B;Dobner, T
通讯作者：
Dobner, T
DOI：
10.1073/pnas.0914605107
发表时间：
2010-07-06
影响因子：
11.1
作者：
Blackford, Andrew N.;Patel, Rakesh N.;Turnell, Andrew S.
通讯作者：
Turnell, Andrew S.