Regulation of telomerase by human papillomaviruses

被引：20

作者：

Galloway, D. A. ^{[1
]}

Gewin, L. C. ^{[1
]}

Myers, H. ^{[1
]}

Luo, W. ^{[1
]}

Grandori, C. ^{[1
]}

Katzenellenbogen, R. A. ^{[1
]}

McDougall, J. K. ^{[1
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Program Canc Biol, Div Human Biol, Seattle, WA 98109 USA

来源：

MOLECULAR APPROACHES TO CONTROLLING CANCER | 2005年 / 70卷

关键词：

D O I：

10.1101/sqb.2005.70.041

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The E6 oncoprotein of human papillomaviruses (HPVs) induces telomerase activity in primary human epithelial cells. This activity is dependent on association of E6 with E6AP, a cellular ubiquitin ligase. E6 activates the transcription of hTERT, the catalytic subunit of telomerase. E boxes near the start of h TERT transcription are required for E6; however, acetylated histones are only present in the E6 cells. We identified two isoforms of NFX1, a new binding partner of E6/E6AP. The NFX1-91 isoform binds to an X-box motif located adjacent to the proximal E box, binds Sin3A and HDACs, repressing hTERT transcription. It preferentially binds E6/E6AP and is targeted for ubiquitin-mediated degradation. The NFX1-123 isoform has the opposite activity, increasing hTERT transcription or translation. This is the first example of viral oncoproteins disrupting regulation of telomerase, a critical event in tumorigenesis.

引用

页码：209 / 215

页数：7

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