XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARα
XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARα
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XPD 基因突变会阻止 TFIIH 依赖核受体的转录激活和 RARα 的磷酸化
DOI：
10.1016/s0092-8674(02)00692-x
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发表时间：
2002-04-05
期刊：
影响因子：
64.5
通讯作者：
Egly, JM
中科院分区：
文献类型：
--
作者：
Keriel, A;Stary, A;Egly, JM
一般转录/修复因子 TFIIH 的 XPD 亚基的遗传突变会产生罕见的遗传性疾病着色性干皮病 (XP)，其表型不能仅根据 DNA 修复缺陷来解释。在来自 XP-D 患者的细胞中，我们观察到由几种核受体（RARα、ERα 和 AR）介导的配体依赖性反式激活减少。我们证明 XPD 突变改变了 RARalpha 磷酸化中的 cdk7 功能。野生型 XPD 或 RARalphaS77E（模拟磷酸化 RARalpha 的突变）过表达后，反式激活就会恢复。因此，我们证明 TFIIH 的 cdk7 激酶磷酸化核受体，然后允许配体依赖性控制激素反应基因的激活。
Inherited mutations in the XPD subunit of the general transcription/repair factor TFIIH yield the rare genetic disorder Xeroderma pigmentosum (XP), the phenotypes of which cannot be explained solely on the basis of a DNA repair defect. In cells derived from XP-D patients, we observed a reduction of the ligand-dependent transactivation mediated by several nuclear receptors (RARalpha, ERalpha, and AR). We demonstrate that the XPD mutation alters cdk7 function in RARalpha phosphorylation. Transactivation is restored upon overexpression of either the wild-type XPD or the RARalphaS77E (a mutation which mimics phosphorylated RARalpha). Thus, we demonstrate that the cdk7 kinase of TFIIH phosphorylates the nuclear receptor, then allowing ligand-dependent control of the activation of the hormone-responsive genes.