NKX-3.1 interacts with prostate-derived Ets factor and regulates the activity of the PSA promoter.
The NKX-3.1 homeobox gene maps to human chromosome 8p21, a region that undergoes frequent loss of heterozygosity in prostate tumors. Loss of Nkx-3.1 function in mice leads to epithelial overgrowth. To further elucidate the molecular basis of NKX-3.1 function, a genetic screen for proteins that interact with NKX-3.1 was performed. Prostate-derived Ets factor (PDEF) was identified as a potential partner of NKX-3.1. Coimmunoprecipitation analyses demonstrated that NKX-3.1 and PDEF are physically associated in prostate epithelial cells. Cotransfection analyses demonstrated that NKX-3.1 can abolish the transcriptional activation function of PDEF on the prostate-specific antigen (PSA) promoter. These data identify PSA as a target gene for NKX-3.1 and provide new insights into the function of this candidate tumor suppressor.
Chen
Hui
H
Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
Nandi
Asit K
AK
Li
Xiang
X
Bieberich
Charles J
CJ
D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000378:metabolism* / Q000502:physiology; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human; D014157:Transcription Factors; D017430:Prostate-Specific Antigen