SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on a functional nuclear localization signal

J Biol Chem. 2005 Jun 10;280(23):21942-8. doi: 10.1074/jbc.M501677200. Epub 2005 Apr 11.

Abstract

SUMO (small ubiquitin-like modifier) is a member of the ubiquitin family of proteins. SUMO targets include proteins involved in numerous roles including nuclear transport and transcriptional regulation. The previous finding that mutant ataxin-1[82Q] disrupted promyelocytic leukemia (PML) oncogenic domains prompted us to determine whether ataxin-1 disrupts another component of PML oncogenic domains, Sp100 (100-kDa Speckled protein). Similar to the PML protein, mutant ataxin-1[82Q] redistributed Sp100 to mutant ataxin-1[82Q] nuclear inclusions. Based on the ability of PML and Sp100 to be covalently modified by SUMO, we investigated the ability of ataxin-1 to be SUMOylated. SUMO-1 was found to covalently modify the polyglutamine repeat protein ataxin-1. There was a decrease in ataxin-1 SUMOylation in the presence of the expanded polyglutamine tract, ataxin-1[82Q]. The phospho-mutant, ataxin-1[82Q]-S776A, restored SUMO levels to those of wild-type ataxin-1[30Q]. SUMOylation of ataxin-1 was dependent on a functional nuclear localization signal. Ataxin-1 SUMOylation was mapped to at least five lysine residues. Lys(16), Lys(194) preceding the polyglutamine tract, Lys(610)/Lys(697) in the C-terminal ataxin high mobility group domain, and Lys(746) all contribute to ataxin-1 SUMOylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Motifs
  • Animals
  • Antigens, Nuclear / metabolism
  • Ataxin-1
  • Ataxins
  • Autoantigens / metabolism
  • Binding Sites
  • COS Cells
  • Cell Line
  • Cell Nucleus / metabolism*
  • Detergents / pharmacology
  • Immunoprecipitation
  • Lysine / chemistry
  • Microscopy, Fluorescence
  • Neoplasm Proteins / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Localization Signals
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Octoxynol / pharmacology
  • Peptides / chemistry
  • Peptides / metabolism*
  • Phosphorylation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • Tumor Suppressor Proteins

Substances

  • ATXN1 protein, human
  • Antigens, Nuclear
  • Ataxin-1
  • Ataxins
  • Autoantigens
  • Detergents
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Peptides
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • SP100 protein, human
  • polyglutamine
  • Octoxynol
  • Lysine