Function of steroidogenic factor 1 (SF1) ligand-binding domain in gene activation and interaction with AP1.
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.
Li
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LA
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Lala
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D
Chung
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D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051717:Fushi Tarazu Transcription Factors; D006066:Gonads / Q000196:embryology / Q000502:physiology; D018398:Homeodomain Proteins; D006801:Humans; D007031:Hypothalamus / Q000196:embryology / Q000502:physiology; D051379:Mice; D009154:Mutation; D010544:Peroxidases; D054464:Peroxiredoxins; D010902:Pituitary Gland / Q000196:embryology / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013963:Thyroid Hormones / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013963:Thyroid Hormones; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D010544:Peroxidases; D054464:Peroxiredoxins