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Role of peroxiredoxin 5 in the de‐silencing of human BRCA2 gene expression
Author(s) -
Turner Jessica Ann,
Misra Smita,
Chaudhuri Gautam
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a81-d
Subject(s) - gene silencing , repressor , biology , microbiology and biotechnology , silencer , slug , gene , gene expression , binding protein , regulation of gene expression , cancer research , genetics , mechanical engineering , engineering , inlet
The tumor suppressor protein BRCA2 is essential for the regulated and synchronized growth of human breast cells in the developing breast tissues. While expression of this protein in the non‐dividing breast cells may induce apoptosis, its proportional expression with the growth rate of the breast cells seems to be vital to prevent malignant transformations of these cells. Indeed BRCA2 gene is not expressed in the non‐dividing human breast cells and it is only expressed in the dividing stages of the cells. We recently have shown that the binding of the repressor protein SLUG to a silencer sequence located at the upstream of human BRCA2 gene promoter silences BRCA2 gene expression in the non‐dividing breast cells (JBC, 280, 17163‐17171). Here we present our preliminary data on how the silencer is inactivated in the dividing breast cells. Analysis of nucleotide sequences of the silencer revealed possible competitive binding of peroxiredoxin 5 to the SLUG binding site of the silencer. A protein of size similar to that from one of the splice variants of peroxiredoxin 5 is pulled down from the nuclear extract of dividing human breast cells instead of SLUG. We are characterizing this purified protein for its binding to the silencer DNA in vitro by EMSA and supershift analysis and in vivo by ChIP assay. These data add to our notion that BRCA2 gene expression in the dividing human breast cells is desilenced by the sequestration of the binding of the repressor protein SLUG by peroxiredoxin 5 at the BRCA2 gene silencer. Supported by the MMC/VICC cancer partnership grant #1U54CA091408‐010003 from NCI and the DOD grant # DAMD17‐00‐1‐0341 to GC.