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Updated: Jun 12, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest

Margaret E Harley1, Lindsey A Allan, Helen S Sanderson

  • 1Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK.

The EMBO Journal
|June 8, 2010
PubMed

Insights

The anti-apoptotic protein Mcl-1 levels peak during mitosis and are degraded via phosphorylation by CDK1-cyclin B1, initiating apoptosis if mitosis is prolonged. This links apoptosis regulation to mitotic progression and arrest.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cell cycle progression and apoptosis are crucial for genomic integrity and drug response.
  • The balance between cell division and programmed cell death is tightly regulated.

Purpose of the Study:

  • To investigate the cell cycle regulation of the anti-apoptotic protein Mcl-1.
  • To determine the role of Mcl-1 phosphorylation and degradation in mitotic arrest and apoptosis induction.

Main Methods:

  • Cell synchronization and arrest using microtubule poisons.
  • Phosphorylation site analysis of Mcl-1.
  • Mutagenesis studies of Mcl-1 phosphorylation sites and destruction motifs.
  • Assessment of proteasome activity and APC/C(Cdc20) involvement.

Main Results:

  • Mcl-1 levels peak at mitosis and are phosphorylated at Ser64 and Thr92.
  • Phosphorylation of Thr92 by CDK1-cyclin B1 triggers Mcl-1 degradation via the APC/C(Cdc20) ubiquitin ligase.
  • Stabilization of Mcl-1 during mitotic arrest prevents apoptosis induction by microtubule poisons.

Conclusions:

  • Mcl-1 degradation is a key event initiated by CDK1-cyclin B1 phosphorylation during prolonged mitotic arrest.
  • This mechanism links apoptosis regulation intrinsically to mitotic progression, distinguishing normal mitosis from arrest.
  • Temporal control of Mcl-1 levels governs the cellular response to mitotic stress.

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