UNLIGANDED T3R, BUT NOT ITS ONCOGENIC VARIANT, V-ERBA, SUPPRESSES RAR-DEPENDENT TRANSACTIVATION BY TITRATING OUT RXR

被引:90
作者
BARETTINO, D
BUGGE, TH
BARTUNEK, P
RUIZ, MDMV
SONNTAGBUCK, V
BEUG, H
ZENKE, M
STUNNENBERG, HG
机构
[1] EMBL,GENE EXPRESS PROGRAMME,MEYERHOFSTR 1,W-6900 HEIDELBERG,GERMANY
[2] IMP,A-1030 VIENNA,AUSTRIA
关键词
ERYTHROID DIFFERENTIATION; ONCOGENE; RAR; RXR; T3R; V-ERBA;
D O I
10.1002/j.1460-2075.1993.tb05779.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
V-erbA is thought to be an antagonist of thyroid hormone receptor (T3R) function. Here we show that unliganded T3R, but not v-erbA, suppresses retinoic acid (RA)-dependent induction of the RAR-beta2 promoter by competing for the common dimerization partner, the retinoid X receptor (RXR). Firstly, T3R suppression can be alleviated by co-transfection of RXR. Secondly, T3R, but not v-erbA, competes with RAR for RXR and causes the dissociation of a preformed RAR/RXR-RARE ternary complex in vitro. A single point mutation located in the dimerization interface of v-erbA (Pro349 to Ser) abolishes the transdominant phenotype when introduced at the respective position in T3R. The hypertransforming v-erbA variant r12, in which this mutation is reversed (Ser349 to Pro) suppresses RA-induced differentiation in chicken erythroid progenitors, while v-erbA does not. Our data thus suggest that unliganded T3R and v-erbA act as dominant suppressors through mechanistically distinct pathways.
引用
收藏
页码:1343 / 1354
页数:12
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