针对p53的降解,HPV E6的序列与p53结合和转激活所需的序列不同
T Crook1, J A Tidy, K H Vousden
1Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, England.
Cell
|November 1, 1991
概括
来自致癌类型的人类乳头瘤病毒 (HPV) 上蛋白E6降解瘤抑制剂p53,而来自良性类型的人类乳头瘤病毒 (HPV) 上蛋白E6结合但不降解p53. 这种差异在于E6蛋白的特定N端序列.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 人类乳头瘤病毒 (HPV) 类型16和18与前生殖器癌症有关.
- HPV 瘤蛋白 E6 针对细胞瘤抑制剂 p53 的降解.
- 类型6和11的HPV通常与良性病变有关.
研究的目的:
- 研究瘤性和良性HPV类型的E6蛋白与p53.3相互作用并影响p53.3的差异性机制.
- 确定负责p53结合和降解的E6蛋白的特定区域.
主要方法:
- 在体外关联试验测试以测试E6-p53复合物形成.
- 功能性测试,以评估由不同E6变体介导的p53降解.
- 对保存的E6蛋白区域 (C端和N端) 进行功能相关性的分析.
主要成果:
- 来自瘤和良性HPV类型的E6蛋白在体外与p53结合.
- 只有来自瘤性HPV类型 (如HPV16) 的E6蛋白有效向p53进行降解.
- 保存的E6的C端区域对于p53结合至关重要.
- 在瘤性HPV类型中保留的特定N终端序列对于指导p53降解至关重要.
- 对于E6介导的p53降解,p53结合是必要的,但不够的.
- E6蛋白的转录转激活活性与p53结合或降解能力无关.
结论:
- HPV E6 coproteins 诱导 p53 降解的能力仅限于瘤性 HPV 类型,并取决于特定的 N-终端序列.
- 通过E6蛋白与p53的差异性相互作用有助于各种HPV类型的独特致癌潜力.
- 了解这些分子机制是开发向癌症预防和治疗的关键.
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