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A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20.

In addition to allelic mutations, cancers are known to harbor alterations in their chromatin landscape. Here we show that genomic ablation of Smad ubiquitin regulatory factor 2 (Smurf2), a HECT-domain E3 ubiquitin ligase, results in dysregulation of both the DNA damage response and genomic stability, culminating in increased susceptibility to various types of cancers in aged mice. We show that Smurf2 regulates the monoubiquitination of histone H2B as well as the trimethylation of histone H3 at Lys4 and Lys79 by targeting ring finger protein 20 (RNF20) for proteasomal degradation in both mouse and human cells. We also show that Smurf2 and RNF20 are colocalized at the γ-H2AX foci of double-stranded DNA breaks in the nucleus. Thus, Smurf2 has a tumor suppression function that normally maintains genomic stability by controlling the epigenetic landscape of histone modifications through RNF20.

Pubmed ID: 22231558

Authors

  • Blank M
  • Tang Y
  • Yamashita M
  • Burkett SS
  • Cheng SY
  • Zhang YE

Journal

Nature medicine

Publication Data

February 7, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: ZIA BC011168-02
  • Agency: NCI NIH HHS, Id: ZIA BC011168-03

Mesh Terms

  • Animals
  • Chromatin
  • DNA Breaks, Double-Stranded
  • DNA Damage
  • DNA Methylation
  • DNA Repair
  • Genes, Tumor Suppressor
  • Histones
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms
  • Ubiquitin-Protein Ligases
  • Ubiquitination