MOUSE RETINOID-X RECEPTOR CONTAINS A SEPARABLE LIGAND-BINDING AND TRANSACTIVATION DOMAIN IN ITS E-REGION

被引:93
作者
LENG, XH
BLANCO, J
TSAI, SY
OZATO, K
OMALLEY, BW
TSAI, MJ
机构
[1] BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030
[2] NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892
关键词
D O I
10.1128/MCB.15.1.255
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
Steroid, thyroid, and retinoid hormones exert their biological functions by interacting with their cognate nuclear receptors. Upon binding receptors, hormones induce a protease-resistant structural change in the receptor ligand-binding domain and subsequently activate the receptors. Utilizing partial proteolysis, we have been able to delineate a region in the mouse retinoid X receptor beta (mRXR beta) required for ligand binding. A separable activation domain within the mRXR beta E region has been identified. The activation domain, which is 21 amino acids in length, is located at the extreme C terminus of mRXR beta. This domain is not required for ligand binding since removal of this sequence neither eliminates the ligand-induced, protease-resistant conformational change nor alters the ligand-enhanced DNA binding. Furthermore, deletion of this activation domain converts the receptor into a transcriptional silencer. Finally, a further truncation of 9 amino acids (for a total of 30 amino acids) from the C terminus results in a mutant which does not undergo the protease-resistant conformational change and cannot bind DNA as a homodimer. Nevertheless, this mutant is still able to form a heterodimer with the thyroid hormone receptor. Therefore, homodimerization and heterodimerization can be distinguished by this nine-amino-acid sequence.
引用
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页码:255 / 263
页数:9
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