Understanding the Mechanism of Action of Breast Metastasis Suppressor BRMS1

Abstract

The focus of this study is to understand the biology behind the metastasis suppression via BRMSl, a recently identified metastasis suppressor gene. BRMSl is a protein with a glutamic acid rich N-terminus, coiled-coil domain, an imperfect leucine zipper and nuclear localization signals. It is expressed almost ubiquitously in human tissues and is highly conserved across species. Sub- cellular fractionation and fluorescence immuno-cytochemistry has indicated that it localizes to nucleus. BRMSl is shown to restore homotypic gap-junctional communication. Our hypothesis is that it may be involved in transcription regulatory complex. To identify proteins that interacting with BRMSl a yeast two-hybrid screen was performed using full length BPNSl as a bait and human mammary gland library as a prey. We confirmed RBPl (Rh binding protein), FLJOOOS2 (EST), MRJ (Hsp4O related chaperon) and Nmi (N-myc interactor) as potential interactors at cellular level by co-immunoprecipitation studies. We have further demonstrated that BRMSl is a component of mSin3-HDAC complex. Based on these observations it is tempting to speculate that BRMSl regulates gene expression by histone deacetylation. Currently we are studying the role of this complex in regulation of metastasis of breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA418406

Entities

People

  • Rajeev S Samant

Organizations

  • University of Alabama

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Breast Cancer
  • Cancer
  • Carrier Proteins
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Enzyme Inhibitors
  • Gene Expression
  • Genetics
  • Health Services
  • Mammary Glands
  • Molecules
  • Neoplasms
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics