BAP18 coactivates androgen receptor action and promotes prostate cancer progression.

Abstract

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.

• Authors: Shiying Sun, Xinping Zhong, Chunyu Wang, Hongmiao Sun, Shengli Wang, Tingting Zhou, Renlong Zou, Lin Lin, Ning Sun, Ge Sun, Yi Wu, Botao Wang, Xiaoyu Song, Liu Cao, Yue Zhao
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 44 Issue 17 Pg. 8112-28 (09 30 2016) ISSN: 1362-4962 [Electronic] England
• PMID: 27226492 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• AR protein, human
• C17orf49 protein, human
• Carrier Proteins
• DNA-Binding Proteins
• KMT2A protein, human
• Proteins
• RNA, Messenger
• Receptors, Androgen
• Myeloid-Lymphoid Leukemia Protein
• Histone-Lysine N-Methyltransferase

Topics

• Amino Acid Sequence
• Animals
• Carrier Proteins (chemistry, genetics, metabolism)
• Cell Line, Tumor
• DNA-Binding Proteins
• Disease Progression
• Drosophila melanogaster (metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• HEK293 Cells
• Histone-Lysine N-Methyltransferase (metabolism)
• Humans
• Male
• Mice
• Myeloid-Lymphoid Leukemia Protein (metabolism)
• Promoter Regions, Genetic (genetics)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Protein Binding
• Proteins (chemistry, genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Androgen (metabolism)
• Transcriptional Activation (genetics)
• Up-Regulation (genetics)
• Xenograft Model Antitumor Assays