The serine/arginine-rich protein SF2/ASF regulates protein sumoylation

Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16119-24. doi: 10.1073/pnas.1004653107. Epub 2010 Aug 30.


Protein modification by conjugation of small ubiquitin-related modifier (SUMO) is involved in diverse biological functions, such as transcription regulation, subcellular partitioning, stress response, DNA damage repair, and chromatin remodeling. Here, we show that the serine/arginine-rich protein SF2/ASF, a factor involved in splicing regulation and other RNA metabolism-related processes, is a regulator of the sumoylation pathway. The overexpression of this protein stimulates, but its knockdown inhibits SUMO conjugation. SF2/ASF interacts with Ubc9 and enhances sumoylation of specific substrates, sharing characteristics with already described SUMO E3 ligases. In addition, SF2/ASF interacts with the SUMO E3 ligase PIAS1 (protein inhibitor of activated STAT-1), regulating PIAS1-induced overall protein sumoylation. The RNA recognition motif 2 of SF2/ASF is necessary and sufficient for sumoylation enhancement. Moreover, SF2/ASF has a role in heat shock-induced sumoylation and promotes SUMO conjugation to RNA processing factors. These results add a component to the sumoylation pathway and a previously unexplored role for the multifunctional SR protein SF2/ASF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Heat-Shock Response
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • SUMO-1 Protein / metabolism*
  • Serine-Arginine Splicing Factors
  • Substrate Specificity
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism


  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • SUMO-1 Protein
  • Tumor Suppressor Protein p53
  • Serine-Arginine Splicing Factors
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9