SUMO modification of repression domains modulates function of nuclear receptor 5A1 (steroidogenic factor-1)

J Biol Chem. 2004 Sep 10;279(37):38730-5. doi: 10.1074/jbc.M405006200. Epub 2004 Jun 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Nucleus / metabolism
  • DNA / chemistry
  • DNA-Binding Proteins / metabolism*
  • Fushi Tarazu Transcription Factors
  • Green Fluorescent Proteins
  • Homeodomain Proteins
  • Immunoblotting
  • Luciferases / metabolism
  • Luminescent Proteins / metabolism
  • Lysine / chemistry
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mutation
  • NIH 3T3 Cells
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cytoplasmic and Nuclear
  • SUMO-1 Protein / metabolism*
  • Steroidogenic Factor 1
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection

Substances

  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • Luminescent Proteins
  • Receptors, Cytoplasmic and Nuclear
  • SUMO-1 Protein
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse
  • Green Fluorescent Proteins
  • DNA
  • Luciferases
  • Lysine