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Updated: May 28, 2026

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06:21

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration

Published on: April 27, 2018

VprBP drives prostate tumorigenesis by its kinase activity targeting histone H2A

Sungmin Kim1, Yonghwan Shin1, Nikhil B Ghate1

  • 1Department of Cancer Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.

Cell Communication and Signaling : CCS
|May 27, 2026
PubMed

Insights

VprBP (Vpr binding protein) is a promising drug target that inactivates growth genes in prostate cancer. A new inhibitor, B0045, effectively blocks VprBP, reduces cancer cell proliferation, and impairs tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • VprBP (Vpr binding protein) is an oncogenic kinase implicated in various human cancers.
  • Its precise mechanism for substrate selectivity in a cancer-dependent manner remains unclear.
  • VprBP phosphorylates histone H2A and other proteins, influencing gene expression.

Purpose of the Study:

  • To investigate the role of VprBP in prostate cancer.
  • To identify and characterize novel, potent VprBP inhibitors for therapeutic development.
  • To elucidate the mechanism of VprBP-mediated gene inactivation in prostate cancer.

Main Methods:

  • Investigated VprBP expression and activity in prostate cancer cells.
  • Utilized kinase assays to assess VprBP activity and phosphorylation of H2AT120.
  • Screened small molecule compounds to identify potent VprBP inhibitors.
  • Evaluated the efficacy of the inhibitor B0045 in vitro and in vivo prostate cancer models.

Main Results:

  • VprBP is highly expressed in prostate cancer and inactivates growth-regulatory genes via H2AT120 phosphorylation.
  • Identified B0045 as a potent second-generation VprBP inhibitor, superior to B32B3.
  • B0045 effectively blocks VprBP kinase activity, reactivates silenced genes, and reduces prostate cancer cell proliferation.
  • B0045 treatment impaired prostate tumor growth in xenograft mouse models.

Conclusions:

  • VprBP-mediated H2AT120 phosphorylation is crucial for oncogenic gene silencing in prostate cancer.
  • B0045 represents a promising therapeutic strategy for targeting VprBP in prostate cancer treatment.
  • Further development of VprBP inhibitors like B0045 holds potential for cancer therapy.
Keywords:
CancerHistoneInhibitorKinasePhosphorylationVprBP

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