25-10-2012, 11:05 AM
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 BRMS1, a recently identified
metastasis suppressor gene. BRMS1 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.
BRMS1 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 BRMS1 a yeast two-hybrid screen was performed
using full length BRMS1 as a bait and human mammary gland library as a prey. We confirmed RBP1 (Rb binding protein),
FLJ00052 (EST), MRJ (Hsp40 related chaperon) and Nmi (N-myc interactor) as potential interactors at cellular level by
co-immunoprecipitation studies.We have further demonstrated that BRMS1 is a component of mSin3-HDAC complex. Based
on these observations it is tempting to speculate that BRMS1 regulates gene expression by histone deacetylation. Currently
we are studying the role of this complex in regulation of metastasis of breast cancer.