2. Academic Validation
  3. Histone H3 phospho-regulation by KimH3 in both interphase and mitosis

Histone H3 phospho-regulation by KimH3 in both interphase and mitosis

  • iScience. 2023 Mar 10;26(4):106372. doi: 10.1016/j.isci.2023.106372.
Junjun Wang 1,  Xiaofei Tian 2,  Chuanlin Feng 1 3,  Chao Song 1,  Biao Yu 1,  Ying Wang 1 3,  Xinmiao Ji 1,  Xin Zhang 1 2 3
Affiliations

Affiliations

  • 1 CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, High Magnetic Field Laboratory of Chinese Academy of Sciences (CHMFL), HFIPS, Hefei, Anhui 230031, P. R. China.
  • 2 Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, P. R. China.
  • 3 Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, Anhui 230036, P. R. China.
PMID: 37013187 DOI: 10.1016/j.isci.2023.106372
Abstract

Histone H3 is phosphorylated at Ser10 by multiple kinases, and many of them are anti-cancer targets. Here, we report the first kinase that can phosphorylate H3Ser10 in both interphase and Mitosis, which we named KimH3 (kinase of interphase and mitotic Histone H3). Meta-analysis indicates that KimH3 is upregulated in a broad spectrum of human cancers and its high expression is correlated with reduced the median survival time of Cancer patients. In Mitosis, CDK1 phosphorylates KimH3, which then phosphorylates H3Ser10 to regulate cell cycle procession. In interphase, EGF induces KimH3 activation and H3Ser10 phosphorylation, which is involved in MAPK-ERK1/2 signaling pathway to activate immediate-early genes transcription. Consequently, a small molecule inhibitor of KimH3 significantly inhibited tumor growth in mice. This is not only consistent with the dual roles of KimH3 in both interphase and mitotic Histone H3 phosphorylation, but also reveals it as an important potential anti-cancer target.

Keywords

Cell biology; Molecular biology.

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