XPD突变阻止了核受体对TFIIH的依赖性交换激活和RARalpha的酸化
Anne Keriel1, Anne Stary, Alain Sarasin
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C. U., Strasbourg, France.
Cell
|April 17, 2002
概括
与Xeroderma pigmentosum (XP) 相关的XPD基因突变损害了超出DNA修复范围的核受体功能. 这项研究揭示了XPD.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- Xeroderma pigmentosum (XP) 是一种罕见的遗传疾病,由XPD基因的突变引起,XPD基因是转录/修复因子TFIIH的组成部分.
- XP表型表明XPD在DNA修复之外的作用,但这些尚未完全理解.
研究的目的:
- 为了研究XPD基因的非DNA修复功能.
- 探索XPD突变对核受体介导的交换激活的影响.
主要方法:
- 从XP-D患者的细胞中分析核受体交换活化.
- 研究XPD在RARalpha核受体酸化中的作用.
- 利用野生型XPD的过度表达和突变的RARalpha (RARalphaS77E) 来评估功能恢复.
主要成果:
- XPD突变减少了核受体的依赖于连接体的交换活化,如RARalpha,ERalpha和AR.
- 在TFIIH中,XPD突变会损害cdk7激酶活性,影响RARalpha酸化.
- 在野生类型的XPD或RARalphaS77E中观察到事务活化的恢复,这表明适当的RARalpha酸化的重要性.
结论:
- TFIIH的XPD亚单元在通过酸化调节核受体活性方面发挥着至关重要的作用.
- 这种由cdk7激酶介导的酸化对于依赖联体的基因激活至关重要.
- XPD的功能超出了DNA修复的范围,影响激素基因调节,并可能导致XP表型.
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