GATA-binding protein 1 is a novel transcription regulator of peroxiredoxin             5 in human breast cancer cells.
Peroxiredoxin 5 (Prx5) is a member of a family consisting of six antioxidant             enzymes. Prx5 is ubiquitously expressed in various tissues including mitochondria             and peroxisomes, implying that Prx5 functions as a regulator of the cellular oxidation             state. Prx5 plays a critical role in protecting cells from oxidative stress by             inhibiting the accumulation of reactive oxygen species and cell death. Overexpression             of Prx5 in mammary tissue is associated with poor prognosis of breast cancer.             The present study was conducted to elucidate the regulatory mechanisms of Prx5             gene expression and the physiological relevance of Prx5 in breast cancer cell             survival. Analysis of the promoter region of the Prx5 gene and reporter gene assays             revealed the promoter region critical for Prx5 gene regulation to which the novel             negative transcription regulator, GATA1 binds in human breast cancer cell lines.             GATA1 was further confirmed as a potential transcription factor for Prx5 gene             expression in another set of transfection assays using a reporter gene construct             that contained a mutated GATA1 binding site. Direct binding of GATA1 to the Prx5             promoter was demonstrated using chromatin immunoprecipitation and electrophoretic             mobility shift assays. Finally, functions of Prx5 associated with apoptosis were             examined in two human breast cancer cell lines displaying high levels of either             Prx5 or GATA1 expression. Knockdown of GATA1 led to increased expression of Prx5             and inhibition of apoptosis. Our data suggest that Prx5 may protect cells from             oxidative stress-mediated apoptosis in a GATA1-regulated manner.
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
Min Ji
MJ
Seo
Xiyuan
X
Liu
Minsun
M
Chang
Jong Hoon
JH
Park
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques / Q000379:methods; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D054464:Peroxiredoxins