SUMOylation of pontin chromatin-remodeling complex reveals a signal integration code in prostate cancer cells

Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20793-8. doi: 10.1073/pnas.0710343105. Epub 2007 Dec 17.

Abstract

Posttranslational modification by small ubiquitin-like modifier (SUMO) controls diverse cellular functions of transcription factors and coregulators and participates in various cellular processes including signal transduction and transcriptional regulation. Here, we report that pontin, a component of chromatin-remodeling complexes, is SUMO-modified, and that SUMOylation of pontin is an active control mechanism for the transcriptional regulation of pontin on androgen-receptor target genes in prostate cancer cells. Biochemical purification of pontin-containing complexes revealed the presence of the Ubc9 SUMO-conjugating enzyme that underlies its function as an activator. Intriguingly, 5alpha-dihydroxytestosterone treatments significantly increased the SUMOylation of pontin, and SUMOylated pontin showed further activation of a subset of nuclear receptor-dependent transcription and led to an increase in proliferation and growth of prostate cancer cells. These data clearly define a functional model and provide a link between SUMO modification and prostate cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Carrier Proteins / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Chromatin / chemistry*
  • DNA Helicases / chemistry*
  • Humans
  • Hydroxytestosterones / pharmacology
  • Lysine / chemistry
  • Male
  • Models, Biological
  • Prostatic Neoplasms / metabolism*
  • SUMO-1 Protein
  • Signal Transduction
  • Small Ubiquitin-Related Modifier Proteins / chemistry*
  • Transcription, Genetic
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Carrier Proteins
  • Chromatin
  • Hydroxytestosterones
  • SUMO-1 Protein
  • SUMO1 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitin-Conjugating Enzymes
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human
  • ubiquitin-conjugating enzyme UBC9
  • Lysine