Covalent modification of a cysteine residue in the XPB subunit of the general transcription factor TFIIH through single epoxide cleavage of the transcription inhibitor triptolide.
Covalent modification of a cysteine residue in the XPB subunit of the general transcription factor TFIIH through single epoxide cleavage of the transcription inhibitor triptolide.
复制标题
DOI：
10.1002/anie.201408817
复制
发表时间：
2015-02-02
影响因子：
16.6
通讯作者：
Liu, Jun O.
中科院分区：
文献类型：
--
作者：
He, Qing-Li;Titov, Denis V.;Li, Jing;Tan, Minjia;Ye, Zhaohui;Zhao, Yingming;Romo, Daniel;Liu, Jun O.
雷公藤内酯醇是中国传统药用植物雷神藤的主要成分，具有很强的抗癌和免疫抑制活性。它是通过共价修饰XPB（一般转录因子TFIIH的亚基）的真核转录的不可逆抑制剂。XPB的Cys 342被鉴定为通过雷公藤内酯醇的12，13-环氧基团进行共价修饰的残基。XPB的Cys 342突变为苏氨酸赋予突变蛋白对雷公藤甲素的抗性。在HEK 293 T细胞系中用Cys 342 Thr突变体替换内源性野生型XPB使其对雷公藤甲素完全耐受，从而验证XPB作为雷公藤甲素的生理相关靶点。总之，这些结果加深了我们对雷公藤甲素和XPB之间相互作用的理解，并对未来开发雷公藤甲素的新类似物作为抗癌和免疫抑制药物的领导者具有影响。
Triptolide is a key component of the traditional Chinese medicinal plant Thunder God Vine and has potent anticancer and immunosuppressive activities. It is an irreversible inhibitor of eukaryotic transcription through covalent modification of XPB, a subunit of the general transcription factor TFIIH. Cys342 of XPB was identified as the residue that undergoes covalent modification by the 12,13-epoxide group of triptolide. Mutation of Cys342 of XPB to threonine conferred resistance to triptolide on the mutant protein. Replacement of the endogenous wild-type XPB with the Cys342Thr mutant in a HEK293T cell line rendered it completely resistant to triptolide, thus validating XPB as the physiologically relevant target of triptolide. Together, these results deepen our understanding of the interaction between triptolide and XPB and have implications for the future development of new analogues of triptolide as leads for anticancer and immunosuppressive drugs.
登录
查看更多内容
影响因子：
56.9
作者：
KUPCHAN, SM;SCHUBERT, RM
通讯作者：
SCHUBERT, RM
影响因子：
--
作者：
Griffith, EC;Su, Z;Liu, JO
通讯作者：
Liu, JO
DOI：
10.1073/pnas.0700499104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Leuenroth, Stephanie J.;Okuhara, Dayne;Crews, Craig M.
通讯作者：
Crews, Craig M.
影响因子：
4.8
作者：
Lee, KY;Chang, WT;Rosen, GD
通讯作者：
Rosen, GD
DOI：
10.1126/science.1232033
发表时间：
2013-02-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mali P;Yang L;Esvelt KM;Aach J;Guell M;DiCarlo JE;Norville JE;Church GM
通讯作者：
Church GM