Papillomavirus E2 Growth Suppression Mechanisms

乳头瘤病毒 E2 生长抑制机制

基本信息

  • 批准号:
    8233032
  • 负责人:
  • 金额:
    $ 56.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-04-01 至 2014-03-31
  • 项目状态:
    已结题

项目摘要

The human papillomaviruses (HPVs) are associated with human cervical cancer as well as some other anogenital cancers and some upper airway cancers. Over 140 different HPVs have now been identified and a subset of these have been associated with these cancers. HPVs are classified as either 'high risk1 (HPV 16, 18) or 'low risk' (HPV 6, 11), based on the clinical lesions with which they are associated and the likelihood for these lesions to progress to cancer. Approximately 90 percent of human cervical cancers harbor the DNA of a high risk HPV type from which two viral oncoproteins, E6 and E7, are invariably expressed. One characteristic of HPV related carcinogenic progression is the frequent integration of the viral genome into the human chromosome in the cancer cells in a manner that results in the loss of expression of the viral E2 gene and to high levels of E6/E7 gene expression. The loss of E2 expression is an important step in HPV associated carcinogenic progression since E2 is able to repress the E6/E7 promoter. The loss of E2 results in the derepression of E6 and E7 oncogene expression. Indeed the expression of the full length E2 protein in HPV positive cervical carcinoma cell lines results in a growth arrest and cellular senescence. The consequent loss of E6 and E7 results in the stabilization of p53 and pRB that in turn mediate cellular growth suppression. The mechanisms by which different forms of E2 mediate this repression however have not yet been established and thjs project is designed to identify genes and pathways involved in this transcriptional repression. The first aim is designed to identify genes and pathways involved in E2-mediated repression of the E6/E7 promoter utilizing a non-biased whole genome siRNA screen. The second aim will determine the mechanisms involved in the repression of the E6/E7 viral promoter. This will focus on novel transcription factors and chromatin modifiers that are revealed and validated in the screen. A third aim will identify the factors and mechanisms involved repression of HPV gene expression that is mediated by a second spliced form of E2 (known as E8AE2C) that has not been extensively studied. A final aim will explore the biologic relevance of the cellular genes identified in the E2 and E8AE2C repression screens in HPV infected epithelial cells and in human cancers.
人类乳头瘤病毒(hpv)与人类宫颈癌以及其他一些疾病有关

项目成果

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Peter M Howley其他文献

Peter M Howley的其他文献

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{{ truncateString('Peter M Howley', 18)}}的其他基金

Molecular Biology of Oncogenic Papillomaviruses
致癌乳头瘤病毒的分子生物学
  • 批准号:
    10322439
  • 财政年份:
    2016
  • 资助金额:
    $ 56.72万
  • 项目类别:
Molecular Biology of Oncogenic Papillomaviruses
致癌乳头瘤病毒的分子生物学
  • 批准号:
    10057232
  • 财政年份:
    2016
  • 资助金额:
    $ 56.72万
  • 项目类别:
Molecular Biology of Oncogenic Papillomaviruses
致癌乳头瘤病毒的分子生物学
  • 批准号:
    8952443
  • 财政年份:
    2016
  • 资助金额:
    $ 56.72万
  • 项目类别:
Small Molecule Screen Targeting p53 proteolysis in HPV positive cancers
针对 HPV 阳性癌症中 p53 蛋白水解的小分子筛选
  • 批准号:
    8641680
  • 财政年份:
    2013
  • 资助金额:
    $ 56.72万
  • 项目类别:
Small Molecule Screen Targeting p53 proteolysis in HPV positive cancers
针对 HPV 阳性癌症中 p53 蛋白水解的小分子筛选
  • 批准号:
    8489916
  • 财政年份:
    2013
  • 资助金额:
    $ 56.72万
  • 项目类别:
Papillomavirus E2 Growth Suppression Mechanisms
乳头瘤病毒 E2 生长抑制机制
  • 批准号:
    7647591
  • 财政年份:
    2009
  • 资助金额:
    $ 56.72万
  • 项目类别:
Papillomavirus E2 Functions: Cellular Regulation and Effectors
乳头瘤病毒 E2 功能:细胞调节和效应器
  • 批准号:
    8435813
  • 财政年份:
    2006
  • 资助金额:
    $ 56.72万
  • 项目类别:
Mechanistic Analysis of Papillimavirus E2 Functions
乳头状病毒E2功能的机制分析
  • 批准号:
    7105179
  • 财政年份:
    2006
  • 资助金额:
    $ 56.72万
  • 项目类别:
Mechanistic Analysis of Papillimavirus E2 Functions
乳头状病毒E2功能的机制分析
  • 批准号:
    7772357
  • 财政年份:
    2006
  • 资助金额:
    $ 56.72万
  • 项目类别:
Mechanistic Analysis of Papillimavirus E2 Functions
乳头状病毒E2功能的机制分析
  • 批准号:
    7909331
  • 财政年份:
    2006
  • 资助金额:
    $ 56.72万
  • 项目类别:

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