NFX1与mSin3A/组蛋白去乙酰化酶相互作用，以抑制角质形成细胞中hTERT的转录。
NFX1 interacts with mSin3A/histone deacetylase to repress hTERT transcription in keratinocytes.
作者信息
Xu Mei, Luo Weifeng, Elzi David J, Grandori Carla, Galloway Denise A
机构信息
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
出版信息
Mol Cell Biol. 2008 Aug;28(15):4819-28. doi: 10.1128/MCB.01969-07. Epub 2008 May 27.
Abstract
Transcription of the catalytic subunit of telomerase (hTERT) in keratinocytes can be induced by human papillomavirus type 16 (HPV16) E6/E6AP ubiquitin ligase through degradation of the repressor, NFX1-91. Here, we demonstrate that NFX1-91 interacts with the corepressor complex mSin3A/histone deacetylase (HDAC) at the hTERT promoter. By degrading NFX1-91, E6/E6AP changes the chromatin structure at the hTERT promoter as indicated by enhanced acetylation of histones H3 and H4 as well as dimethylation of H3K4. Knockdown of NFX1-91 by short hairpin RNA (shRNA) mimics the effect of E6 and leads to acetylation of histones H3 and H4. Conversely, knockdown of E6AP by shRNA suppresses histone acetylation at the hTERT promoter. These data demonstrate that targeted degradation of NFX1-91 by E6/E6AP dissociates the mSin3A/HDAC complex from the hTERT promoter and induces hTERT transcription.
摘要
人乳头瘤病毒16型（HPV16）E6/E6相关蛋白（E6AP）泛素连接酶可通过降解阻遏物NFX1-91来诱导角质形成细胞中端粒酶催化亚基（hTERT）的转录。在此，我们证明NFX1-91在hTERT启动子处与共阻遏复合物mSin3A/组蛋白去乙酰化酶（HDAC）相互作用。通过降解NFX1-91，E6/E6AP改变了hTERT启动子处的染色质结构，这表现为组蛋白H3和H4乙酰化增强以及H3K4二甲基化。用短发夹RNA（shRNA）敲低NFX1-91模拟了E6的作用，并导致组蛋白H3和H4乙酰化。相反，用shRNA敲低E6AP可抑制hTERT启动子处的组蛋白乙酰化。这些数据表明，E6/E6AP对NFX1-91的靶向降解使mSin3A/HDAC复合物从hTERT启动子上解离，并诱导hTERT转录。
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本文引用的文献
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