BAP18 coactivates androgen receptor action and promotes prostate cancer progression

BPTF associated protein of 18 kDa (BAP18) has been reported as a component of MLL1-WDR5 complex. However, BAP18 is an uncharacterized protein. The detailed biological functions of BAP18 and underlying mechanisms have not been defined. Androgen receptor (AR), a member of transcription factor, plays a...

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Bibliographic Details
Published in:Nucleic acids research 2016-09, Vol.44 (17), p.8112-8128
Main Authors: Sun, Shiying, Zhong, Xinping, Wang, Chunyu, Sun, Hongmiao, Wang, Shengli, Zhou, Tingting, Zou, Renlong, Lin, Lin, Sun, Ning, Sun, Ge, Wu, Yi, Wang, Botao, Song, Xiaoyu, Cao, Liu, Zhao, Yue
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line, Tumor
Disease Progression
DNA-Binding Proteins
Drosophila melanogaster - metabolism
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene regulation, Chromatin and Epigenetics
HEK293 Cells
Histone-Lysine N-Methyltransferase - metabolism
Humans
Male
Mice
Myeloid-Lymphoid Leukemia Protein - metabolism
Promoter Regions, Genetic - genetics
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Binding
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Receptors, Androgen - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transcriptional Activation - genetics
Up-Regulation - genetics
Xenograft Model Antitumor Assays
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Summary:BPTF associated protein of 18 kDa (BAP18) has been reported as a component of MLL1-WDR5 complex. However, BAP18 is an uncharacterized protein. The detailed biological functions of BAP18 and underlying mechanisms have not been defined. Androgen receptor (AR), a member of transcription factor, plays an essential role in prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) progression. Here, we demonstrate that BAP18 is identified as a coactivator of AR in Drosophilar experimental system and mammalian cells. BAP18 facilitates the recruitment of MLL1 subcomplex and AR to androgen-response element (ARE) of AR target genes, subsequently increasing histone H3K4 trimethylation and H4K16 acetylation. Knockdown of BAP18 attenuates cell growth and proliferation of PCa cells. Moreover, BAP18 depletion results in inhibition of xenograft tumor growth in mice even under androgen-depletion conditions. In addition, our data show that BAP18 expression in clinical PCa samples is higher than that in benign prostatic hyperplasia (BPH). Our data suggest that BAP18 as an epigenetic modifier regulates AR-induced transactivation and the function of BAP18 might be targeted in human PCa to promote tumor growth and progression to castration-resistance.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkw472