TY - JOUR
T1 - Function of steroidogenic factor 1 (SF1) ligand-binding domain in gene activation and interaction with AP1
AU - Li, Lih Ann
AU - Lala, Deepak
AU - Chung, Bon Chu
N1 - Funding Information:
We thank Dr. Keith Parker for the gifts of SF1 mutant plasmids. This work was supported by Grants NSC86-2313-B-001-011 and NSC 87-2311-B-001-127 from the National Science Council and by Academia Sinica, Republic of China.
PY - 1998/9/18
Y1 - 1998/9/18
N2 - The nuclear receptor SF1 is an essential mediator in ventromedial hypothalamus-pituitary-gonadal development. As with other nuclear receptors, SF1 possesses a DNA-binding domain composed of two zinc fingers and a ligand-binding domain containing a ligand-dependent activation sequence termed AF2. To dissect the domain function of SF1, we examined various SF1 mutants in mouse adrenocortical Y1 cells and human placental JEG3 cells. Destruction of the AF2 structure removed 73-90% transactivation activity, suggesting that AF2 is indispensable for transactivation. Mutants carrying the DNA-binding domain but lacking the AF2 or the ligand-binding domain blocked the activity of normal SF1. Disrupting the zinc finger diminished the dominant negative effect of mutant. Cotransfection of SF1 with AP1 showed that the two transcription factors cooperated to activate gene expression. Some mutants lost the synergistic action with AP1, while some retained partial activity. These experiments delineate the functional domains of SF1.
AB - The nuclear receptor SF1 is an essential mediator in ventromedial hypothalamus-pituitary-gonadal development. As with other nuclear receptors, SF1 possesses a DNA-binding domain composed of two zinc fingers and a ligand-binding domain containing a ligand-dependent activation sequence termed AF2. To dissect the domain function of SF1, we examined various SF1 mutants in mouse adrenocortical Y1 cells and human placental JEG3 cells. Destruction of the AF2 structure removed 73-90% transactivation activity, suggesting that AF2 is indispensable for transactivation. Mutants carrying the DNA-binding domain but lacking the AF2 or the ligand-binding domain blocked the activity of normal SF1. Disrupting the zinc finger diminished the dominant negative effect of mutant. Cotransfection of SF1 with AP1 showed that the two transcription factors cooperated to activate gene expression. Some mutants lost the synergistic action with AP1, while some retained partial activity. These experiments delineate the functional domains of SF1.
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U2 - 10.1006/bbrc.1998.9305
DO - 10.1006/bbrc.1998.9305
M3 - Article
C2 - 9753627
AN - SCOPUS:0032544404
SN - 0006-291X
VL - 250
SP - 318
EP - 320
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -