Quantitative proteomic identification of the BRCA1 ubiquitination substrates

Meihua Song, Kevin Hakala, Susan T. Weintraub, Yuzuru Shiio

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Mutation of the BRCA1 tumor suppressor gene predisposes women to hereditary breast and ovarian cancers. BRCA1 forms a heterodimer with BARD1. The BRCA1/BARD1 heterodimer has ubiquitin ligase activity, considered to play crucial roles in tumor suppression and DNA damage response. Nevertheless, relevant BRCA1 substrates are poorly defined. We have developed a new approach to systematically identify the substrates of ubiquitin ligases by identifying proteins that display an enhanced incorporation of His-tagged ubiquitin upon ligase coexpression; using this method, we identified several candidate substrates for BRCA1. These include scaffold attachment factor B2 (SAFB2) and Tel2 as well as BARD1. BRCA1 was found to enhance SAFB protein expression and induce Tel2 nuclear translocation. Identification of the ubiquitination substrates has been a major obstacle to understanding the functions of ubiquitin ligases. The quantitative proteomics approach we devised for the identification of BRCA1 substrates will facilitate the identification of ubiquitin ligase-substrate pairs.

Original languageEnglish (US)
Pages (from-to)5191-5198
Number of pages8
JournalJournal of Proteome Research
Issue number11
StatePublished - Nov 4 2011


  • BARD1
  • BRCA1
  • quantitative proteomics
  • substrate
  • ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)


Dive into the research topics of 'Quantitative proteomic identification of the BRCA1 ubiquitination substrates'. Together they form a unique fingerprint.

Cite this