1. Academic Validation
  2. VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription

VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription

  • Mol Cell. 2013 Nov 7;52(3):459-67. doi: 10.1016/j.molcel.2013.09.017.
Kyunghwan Kim 1 Jin-Man Kim Joong-Sun Kim Jongkyu Choi Yong Suk Lee Nouri Neamati Jin Sook Song Kyu Heo Woojin An
Affiliations

Affiliation

  • 1 Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA; Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
Abstract

Histone modifications play important roles in the regulation of gene expression and chromatin organization. VprBP has been implicated in transcriptionally silent chromatin formation and cell-cycle regulation, but the molecular basis underlying such effects remains unclear. Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. VprBP is localized to a large set of tumor suppressor genes and blocks their transcription, in a manner that is dependent on its kinase activity toward H2AT120. The functional significance of VprBP-mediated H2AT120p is further underscored by the fact that RNAi knockdown and small-molecule inhibition of VprBP reactivate growth regulatory genes and impede tumor growth. Our findings establish VprBP as a major kinase responsible for H2AT120p in Cancer cells and suggest that VprBP inhibition could be a new strategy for the development of Anticancer therapeutics.

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