The Role of BRCA1/BARD1 Heterodimers in the Mitosis-Interphase Transition

Abstract

The study was aimed at exploiting the advantages of the Xenopus egg extract as a biochemically tractable in vitro cell cycle model system in order to elucidate the molecular function of the breast and ovarian tumor suppressor BRCA1 and its hetorodimerizing partner, BARD1. Experiments using both egg extracts and cultured mammalian cells revealed a previously unknown role of BRCA1/BARD1 in the mitotic spindle assembly. This BRCA1/BARD1 function is centrosome-independent, operates downstream of Ran GTPase, and depends upon the E3 ubiquitin ligase activity of the heterodimer. BRCA1/BARD1 ensures proper spindle pole formation by down-modulating the function of a recently discovered TPX2 partner, XRHAMM, thereby facilitating the accumulation of TPX2, the major spindle assembly factor and Ran target, on spindle poles. Our study implicated BRCA1/BARD1 in the regulation of three SAFs (RHAMM, TPX2, and Aurora A), which are overexpressed or amplified in certain cancers, thus pointing to the existence of a tumor suppressoroncoprotein network that controls mitotic spindle assembly.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2007
Accession Number
ADA471801

Entities

People

  • Vladimir Joukov

Organizations

  • Dana–Farber Cancer Institute

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Cytoskeleton
  • Genetics
  • Peptides
  • Proteins
  • Recombinant Proteins
  • Three Dimensional
  • Two Dimensional

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