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Peroxiredoxin 5 (Prx5) is a member of a family consisting of six antioxidantenzymes. Prx5 is ubiquitously expressed in various tissues including mitochondriaand peroxisomes, implying that Prx5 functions as a regulator of the cellular oxidationstate. Prx5 plays a critical role in protecting cells from oxidative stress byinhibiting the accumulation of reactive oxygen species and cell death. Overexpressionof Prx5 in mammary tissue is associated with poor prognosis of breast cancer.The present study was conducted to elucidate the regulatory mechanisms of Prx5gene expression and the physiological relevance of Prx5 in breast cancer cellsurvival. Analysis of the promoter region of the Prx5 gene and reporter gene assaysrevealed the promoter region critical for Prx5 gene regulation to which the novelnegative transcription regulator, GATA1 binds in human breast cancer cell lines.GATA1 was further confirmed as a potential transcription factor for Prx5 geneexpression in another set of transfection assays using a reporter gene constructthat contained a mutated GATA1 binding site. Direct binding of GATA1 to the Prx5promoter was demonstrated using chromatin immunoprecipitation and electrophoreticmobility shift assays. Finally, functions of Prx5 associated with apoptosis wereexamined in two human breast cancer cell lines displaying high levels of eitherPrx5 or GATA1 expression. Knockdown of GATA1 led to increased expression of Prx5and inhibition of apoptosis. Our data suggest that Prx5 may protect cells fromoxidative stress-mediated apoptosis in a GATA1-regulated manner.

GATA-binding protein 1 is a novel transcription regulator of peroxiredoxin 5 in human breast cancer cells