Deleted in breast cancer 1, a novel androgen receptor (AR) coactivator that promotes AR DNA-binding activity.
Androgen receptor (AR) plays a critical role in development and maintenance of male reproductive functions and the etiology of prostate cancer. As a ligand-regulated transcription factor, identification and characterization of AR coregulators are essential for understanding the molecular mechanisms underlying its diverse biological functions. Here we reported the identification of a novel AR coactivator, deleted in breast cancer 1 (DBC1), through a biochemical approach. DBC1 interacts with AR in a ligand-stimulated manner and facilitates AR transcriptional activation in transfected cells as well as in Xenopus oocytes. In in vitro gel shift experiments, recombinant DBC1 drastically enhanced AR DNA-binding activity. Expression of DBC1 also enhanced the binding of AR to chromatinized template in vivo, whereas knockdown of DBC1 impaired the binding of AR to endogenous prostate-specific antigen (PSA) gene in the prostate cancer cell line LNCaP. Thus, our data identify DBC1 as a novel AR coactivator.
Fu
Junjiang
J
The Institute of Biomedical Sciences, College of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
Jiang
Jun
J
Li
Jiwen
J
Wang
Shanshan
S
Shi
Guang
G
Feng
Qin
Q
White
Eileen
E
Qin
Jun
J
Wong
Jiemin
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D014981:Xenopus
C410798:AR protein, human; D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen