Deciphering the Molecular Mechanisms of Breast Cancer

Abstract

We have isolated a holoenzyme complex termed BRCC containing BRCA1, BRCA2, and RAD51. BRCC not only displays increased association with p53 following DNA damage but also ubiquitinates p53 in vitro. BRCC36 and BRCC45 are novel components of the complex with sequence homology to a subunit of the signalosome and proteasome complexes. Reconstitution of a recombinant foursubunit complex containing BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to that of BRCA1/BARD1 heterodimer. In vivo, depletion of BRCC36 and BRCC45 by the small interfering RNAs (siRNAs) resulted in increased sensitivity to ionizing radiation and defects in G2/M checkpoint. BRCC36 shows aberrant expression in sporadic breast tumors. These findings identify BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2005
Accession Number
ADA467787

Entities

People

  • Ramin Shiekhattar

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Brain
  • Breast Cancer
  • Carrier Proteins
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Genetics
  • Health Services
  • Ionizing Radiation
  • Lymphocytes
  • Medical Personnel
  • Neoplasms
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Aerospace Research.
  • Immunology
  • Molecular Biology and Genetics