SUMO modification of repression domains modulates function of nuclear receptor 5A1 (steroidogenic factor-1).
Steroidogenic factor 1 (SF-1 or NR5A1), is a Ftz-F1 member of the nuclear receptor superfamily that plays essential roles in endocrine development, steroidogenesis, and gonad differentiation. We investigated modifications that control SF-1 function and found that SF-1 could be conjugated by SUMO-1 both in vitro and in vivo. SF-1 was modified predominantly at Lys(194) and much less at Lys(119) when free SUMO-1 was supplied. Mutations of Lys(194) and Lys(119) enhanced transcriptional activity of SF-1, although the DNA binding activity of SF-1 was not affected. Sequences around Lys(194) and Lys(119) both repressed transcription intrinsically. The Lys(194) motif repressed transcription more efficiently than the Lys(119) domain, consistent with its ability to be a better substrate for SUMO conjugation. Thus, SUMO modification of SF-1 correlates with transcriptional repression. Wild-type but not conjugation-deficient SF-1 was localized at the nuclear speckles together with SUMO-1. Thus, SUMO-1 conjugation could also target SF-1 into nuclear speckles. Collectively, these results suggest that SUMO modification at the repression domains targets SF-1 to nuclear speckles; this could be an important mechanism by which SF-1 is regulated.
Chen
Wei-Yi
WY
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Lee
Wen-Chih
WC
Hsu
Nai-Chi
NC
Huang
Fu
F
Chung
Bon-Chu
BC
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051717:Fushi Tarazu Transcription Factors; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009154:Mutation; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D025842:SUMO-1 Protein / Q000378:metabolism*; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D025842:SUMO-1 Protein; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D049452:Green Fluorescent Proteins; D004247:DNA; D008156:Luciferases; D008239:Lysine