title: ZMIZ1 preferably enhances the transcriptional activity of androgen receptor with short polyglutamine tract.
abstract: The androgen receptor (AR) is a ligand-induced transcription factor and contains the polyglutamine (polyQ) tracts within its N-terminal transactivation domain. The length of polyQ tracts has been suggested to alter AR transcriptional activity in prostate cancer along with other endocrine and neurologic disorders. Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably augments ARQ9 induced androgen-dependent transcription on three different androgen-inducible promoter/reporter vectors. A strong protein-protein interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9 was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR activity. Using the chromatin immunoprecipitation assays (ChIP), we further demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the prostate specific antigen (PSA) gene. These results demonstrate a novel regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate cancer cells.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California, United States of America. lixm441@nenu.edu.cn
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Li
authors.forename: Chunfang
authors.initials: C
authors.lastname: Zhu
authors.forename: William H
authors.initials: WH
authors.lastname: Tu
authors.forename: Nanyang
authors.initials: N
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Qin
authors.forename: Zijie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D010455:Peptides / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D010455:Peptides; D050828:Protein Inhibitors of Activated STAT; D011944:Receptors, Androgen; D014157:Transcription Factors; C480599:ZMIZ1 protein, human; C507928:ZMIZ2 protein, human; C097188:polyglutamine; D017430:Prostate-Specific Antigen