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Updated: May 20, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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CARM1 S217 phosphorylation by CDK1 in late G2 phase facilitates mitotic entry

Yena Cho1,2, Dae-Geun Song3,4, Su-Nam Kim3,4

  • 1Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

Cell Death & Disease
|March 26, 2025
PubMed

Insights

Coactivator-associated arginine methyltransferase 1 (CARM1) is a novel CDK1 substrate regulating mitosis. Phosphorylation by CDK1 inhibits CARM1, promoting cell cycle entry and accelerated growth.

Area of Science:

  • Epigenetics
  • Cell Cycle Regulation
  • Molecular Biology

Background:

  • Coactivator-associated arginine methyltransferase 1 (CARM1) is known as an epigenetic writer.
  • The precise role of CARM1 during mitosis has not been fully elucidated.
  • Understanding CARM1's function in cell division is crucial for comprehending cell cycle control.

Purpose of the Study:

  • To investigate the role of CARM1 in mitosis.
  • To identify novel regulators and substrates of cyclin-dependent kinase 1 (CDK1) during the cell cycle.
  • To elucidate the molecular mechanisms by which CARM1 influences cell cycle progression.

Main Methods:

  • Substrate identification assays to determine CARM1 as a CDK1 target.
  • Phosphorylation site mapping (S217) using mass spectrometry.
  • Cellular localization studies using immunofluorescence.
  • Depletion and inhibition studies using siRNA and chemical inhibitors.
  • Cell proliferation assays to assess the impact on cell growth.

Main Results:

  • CARM1 was identified as a novel substrate of CDK1, phosphorylated at residue S217.
  • Phosphorylation of CARM1 by CDK1 inhibits its enzymatic activity and promotes its cytoplasmic translocation.
  • CARM1 acts as a scaffold regulating CDK1 stability, limiting its nuclear levels during interphase.
  • Depletion or inhibition of CARM1 accelerates entry into mitosis and enhances cell growth.
  • CDK1/Cyclin B1 complex nuclear residence time is extended by CARM1 phosphorylation, initiating mitosis.

Conclusions:

  • CARM1 possesses a novel scaffolding function that regulates CDK1 stability and nuclear localization.
  • CDK1-mediated phosphorylation of CARM1 is a critical event for timely entry into mitosis.
  • CARM1's function extends beyond its epigenetic writer role, impacting cell cycle progression and growth.

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