Premium
Selective modulation of the redox state and thus the repressor function of SLUG by peroxiredoxin 5 at the BRCA2 gene silencer in human breast cancer cells
Author(s) -
MISRA SMITA,
MITTAL MUKUL K,
CHAUDHURI GAUTAM
Publication year - 2011
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.25.1_supplement.913.3
Subject(s) - slug , repressor , gene silencing , zinc finger , gene , promoter , transcription factor , biology , microbiology and biotechnology , gene expression , cancer research , genetics
Human BRCA2 gene expression is inhibited by the transcriptional repressor protein SLUG at the G0/G1 phase of SLUG‐high breast cancer cells through the binding of SLUG to an E2‐box sequence in the BRCA2 gene. Interestingly, while SLUG maintains its repression of several of its target genes at the S/G2 phase of cell growth, it fails to repress BRCA2 gene at this growth phase. We discovered that, unlike other SLUG target gene promoters, BRCA2 gene silencer has the SLUG‐binding E2‐box at the close proximity of the binding site of the redox modulator protein peroxiredoxin 5 (PRDX5). Here, we provide evidence that in the S/G2 phase of cell growth, oxidized PRDX5 enters the nucleus at a higher rate and binds to BRCA2 silencer to rip off SLUG from its E2‐box through oxidation of its DNA binding zinc finger domains resulting in the de‐silencing of BRCA2 gene expression. This study presents a novel modality of PRDX5 in site‐specific oxidation of zinc‐finger transcription factors to regulate gene expression in a redox‐dependent manner. Supported by DOD‐CDMRP BCRP Grants W81XWH‐06‐1‐0466, W81XWH‐08‐1‐0446, BC086542, and Susan G. Komen Breast Cancer Foundation grant# BCTR0707627 to GC and 1U54RR026140‐01to SM.