Scholarlink

<p>VprBP has been recently identified as an oncogenic kinase and a promising drug target in human malignant tumors. Although VprBP can phosphorylate histone H2A and some non-histone proteins, it seems to selectively target specific substrates in a cancer type-dependent manner by an unknown mechanism. Here we report that VprBP is highly expressed in prostate cancer cells and inactivates a group of genes encoding critical regulators of cell growth and proliferation in a manner dependent on its kinase activity toward H2AT120. As an extension of our previous finding of VprBP inhibitor B32B3, we also screened a series of small molecule compounds derived from B32B3 and identified B0045 as a second-generation VprBP inhibitor with much higher efficacy and potency. B0045 is far more effective in blocking VprBP-mediated H2AT120p and reactivating growth regulatory genes, resulting in a significantly lower proliferative capacity of prostate cancer cells. Similarly, B0045 treatment inhibits VprBP kinase activity, modulates H2AT120p-induced gene inactivation, and impairs prostate tumor growth in xenograft mouse models. Together, our findings establish a critical role for VprBP-mediated H2AT120p in oncogenic gene silencing and B0045 as a promising therapeutic strategy for prostate cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

VprBP drives prostate tumorigenesis by its kinase activity targeting histone H2A

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月26日

查看全文
  • Sungmin Kim,
  • Yonghwan Shin,
  • Nikhil B. Ghate,
  • Woojin An

摘要

VprBP has been recently identified as an oncogenic kinase and a promising drug target in human malignant tumors. Although VprBP can phosphorylate histone H2A and some non-histone proteins, it seems to selectively target specific substrates in a cancer type-dependent manner by an unknown mechanism. Here we report that VprBP is highly expressed in prostate cancer cells and inactivates a group of genes encoding critical regulators of cell growth and proliferation in a manner dependent on its kinase activity toward H2AT120. As an extension of our previous finding of VprBP inhibitor B32B3, we also screened a series of small molecule compounds derived from B32B3 and identified B0045 as a second-generation VprBP inhibitor with much higher efficacy and potency. B0045 is far more effective in blocking VprBP-mediated H2AT120p and reactivating growth regulatory genes, resulting in a significantly lower proliferative capacity of prostate cancer cells. Similarly, B0045 treatment inhibits VprBP kinase activity, modulates H2AT120p-induced gene inactivation, and impairs prostate tumor growth in xenograft mouse models. Together, our findings establish a critical role for VprBP-mediated H2AT120p in oncogenic gene silencing and B0045 as a promising therapeutic strategy for prostate cancer.