VPRBP, a novel androgen receptor and OGT target is an essential mediator of cellular transformation in prostate cancer

Androgen receptor (AR) plays a central role in the development of prostate cancer. Increased expression of O-GlcNAc transferase (OGT) and O-GlcNAcylation are also implicated in metastatic prostate caner. We have identified VPRBP as a novel androgen-regulated gene and the stability of the encoded protein is regulated by OGT.VPRBP downregulation led to significant decrease in cell proliferation and p53 stabilization in LNCaPs. In this study, we employed chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) to identify changes in p53 binding to the genome in VPRBP knockdown LNCaPs compared to scrambled siRNA transfected control cells. Stabilization of p53 was associated increased p53 recruitment to the chromatin. Overall design: ChIP-seq studies were carried out in nutlin-3a treated LNCaPs, and scrambled siRNA vs VPRBP siRNA 1 and VPRBP siRNA 2 transfected LNCaPs using antibody against p53 (Santa Cruz Biotechnology, sc-126)