Silencing subdomains of v-ErbA interact cooperatively with corepressors: involvement of helices 5/6.
Silencing subdomains of v-ErbA interact cooperatively with corepressors: involvement of helices 5/6.
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v-ErbA 的沉默子结构域与辅阻遏物协同相互作用：螺旋 5/6 的参与。
作者：
K. Busch;B. Martin;A. Baniahmad;J. Martial;R. Renkawitz;M. Muller
Members of the thyroid hormone receptor (TR) family act on vertebrate development and homeostasis by activating or repressing transcription of specific target genes in a ligand-dependent way. Repression by TR in the absence of ligand is mediated by an active silencing mechanism. The oncogene v-ErbA is a variant form of TR unable to bind hormone and thus acts as a constitutive repressor. Functional studies and mutation analysis revealed that the TR/v-ErbA silencing domain is composed of three silencing subdomains (SSD1-3) which, although nonfunctional individually, synergize such that silencing activity is restored when they are combined in a heteromeric complex. Here we demonstrate, using protein interaction assays in vitro and in vivo, that the inactive v-ErbA point mutant L489R within helix 5/6 in SSD2 fails to interact with the two corepressors N-CoR (nuclear receptor corepressor) or SMRT (silencing mediator of retinoic acid and thyroid hormone receptor). Furthermore, mutants in SSD1 and SSD3 exhibit a reduced corepressor recruitment corresponding to their weak residual silencing activity. In mammalian two-hybrid assays, only the combination of all three silencing subdomains, SSD1-3, leads to a cooperative binding to the corepressors N-CoR or SMRT comparable to that of the full-length v-ErbA repression domain. In conclusion, full silencing activity requires corepressor interaction with all three silencing subdomains, SSD1-3. Among these, SSD2 is a new target for N-CoR and SMRT and is essential for corepressor binding and function.
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酪氨酸激酶的信号传导负向调节转录因子和 SMRT（视黄酸和甲状腺激素受体沉默介质）辅阻遏物之间的相互作用。
DOI：
10.1210/mend.12.8.0160
发表时间：
1998
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Hong,SH;Wong,CW;Privalsky,ML
通讯作者：
Privalsky,ML
影响因子：
--
作者：
S. Sande;M. Privalsky
通讯作者：
S. Sande;M. Privalsky
核激素受体辅阻遏物 RIP13/N-CoR 中的两个受体相互作用结构域。
DOI：
10.1210/mend.10.12.8961273
发表时间：
1996
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Seol,W;Mahon,MJ;Lee,YK;Moore,DD
通讯作者：
Moore,DD
甲状腺激素受体的一种新的自然突变定义了交换核受体辅阻遏物和共激活物的双重功能域。
DOI：
10.1210/mend.12.12.0201
发表时间：
1998
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Tagami,T;Gu,WX;Peairs,PT;West,BL;Jameson,JL
通讯作者：
Jameson,JL
TATA 结合蛋白相关因子充当甲状腺激素受体的共激活剂。
DOI：
10.1210/mend.10.12.8961272
发表时间：
1996
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Petty,KJ;Krimkevich,YI;Thomas,D
通讯作者：
Thomas,D