The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation

Michal Feldman, Zlata Vershinin, Inna Goliand, Natalie Elia, Dan Levy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Lysine methylation, catalyzed by protein lysine methyltransferases (PKMTs), is a key player in regulating intracellular signaling pathways. However, the role of PKMTs and the methylation of nonhistone proteins during the cell cycle are largely unexplored. In a recent proteomic screen, we identified that the PKMT SETD6 methylates PLK1—a key regulator of mitosis and highly expressed in tumor cells. In this study, we provide evidence that SETD6 is involved in cell cycle regulation. SETD6-deficient cells were observed to progress faster through the different mitotic steps toward the cytokinesis stage. Mechanistically, we found that during mitosis SETD6 binds and methylates PLK1 on two lysine residues: K209 and K413. Lack of methylation of these two residues results in increased kinase activity of PLK1, leading to accelerated mitosis and faster cellular proliferation, similarly to SETD6-deficient cells. Taken together, our findings reveal a role for SETD6 in regulating mitotic progression, suggesting a pathway through which SETD6 methylation activity contributes to normal mitotic pace.

Original languageEnglish
Pages (from-to)1235-1240
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number4
DOIs
StatePublished - 22 Jan 2019

Keywords

  • Cell cycle
  • Lysine methylation
  • Mitosis
  • PLK1
  • SETD6

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