title: Mitogen-activated protein kinase phosphatase 2 regulates histone H3 phosphorylation via interaction with vaccinia-related kinase 1.
abstract: Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate MAP kinase signaling. However, MKP2 functions are still largely unknown. In this study, we showed that MKP2 could regulate histone H3 phosphorylation under oxidative stress conditions. We found that MKP2 inhibited histone H3 phosphorylation by suppressing vaccinia-related kinase 1 (VRK1) activity. Moreover, this regulation was dependent on the selective interaction with VRK1, regardless of its phosphatase activity. The interaction between MKP2 and VRK1 mainly occurred in the chromatin, where histones are abundant. We also observed that the protein level of MKP2 and its interaction with histone H3 increased from G1 to M phase during the cell cycle, which is similar to the VRK1 profile. Furthermore, MKP2 specifically regulated the VRK1-mediated histone H3 phosphorylation at M phase. Taken together, these data suggest a novel function of MKP2 as a negative regulator of VRK1-mediated histone H3 phosphorylation.
authors.affiliation: Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Jeong
authors.forename: Tae-Hong
authors.initials: TH
authors.lastname: Kang
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.forename: Yoon Ha
authors.initials: YH
authors.lastname: Choi
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D002455:Cell Division; D002843:Chromatin / Q000201:enzymology; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D002843:Chromatin; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases