期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 14, 页码 8211-8216出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1435900100
关键词
-
资金
- NCI NIH HHS [R01 CA053371, 1 F31 CA90203-02, F31 CA090203, R01 CA53371, R01 CA106400] Funding Source: Medline
The papillomavirus E6 protein binds and directs the ubiquitin-dependent degradation of the p53 tumor suppressor protein. independent of this p53-degradative function, however, E6 induces cellular telomerase. activity. This increase in enzyme activity reflects E6-enhanced transcription of the human telomerase reverse transcriptase (hTERT) catalytic subunit, but the molecular basis for this transactivation is unknown. In the present study, we demonstrate that E6/Myc interactions regulate hTERT gene expression. Mad protein, a specific antagonist of Myc, repressed E6-mediated transactivation of the hTERT promoter and this repression was relieved by Myc overexpression. The proximal Myc/Max-binding element (E-box) in the hTERT promoter was the major determinant of both E6 and Myc responsiveness in keratinocytes. E6 did not alter Myc protein expression or Myc/Max association, and the induction of hTERT by Myc/E6 was independent of Myc phosphorylation at Thr-58/Ser-62 within the transactivation domain. However, immunoprecipitation studies demonstrated that endogenous Myc protein coprecipitated with E6 protein and chromatin immunoprecipitation analyses demonstrated that both E6 and Myc proteins bound to a minimal 295-bp hTERT promoter. Only the high-risk E6 proteins bound to the hTERT promoter, consistent with their preferential ability to induce telomerase. The observation that E6 associates with Myc complexes and activates a Myc-responsive gene identifies a mechanism by which this oncogene can modulate cell proliferation and differentiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据