SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression

Anita C. Bellail (), Jeffrey J. Olson and Chunhai Hao ()
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Anita C. Bellail: Montreal Neurological Institute and Hospital, McGill University
Jeffrey J. Olson: Emory University School of Medicine
Chunhai Hao: Montreal Neurological Institute & Hospital, McGill University

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Ubiquitination governs oscillation of cyclin-dependent kinase (CDK) activity through a periodic degradation of cyclins for orderly cell cycle progression; however, the mechanism that maintains the constant CDK protein levels throughout the cell cycle remains unclear. Here we show that CDK6 is modified by small ubiquitin-like modifier-1 (SUMO1) in glioblastoma, and that CDK6 SUMOylation stabilizes the protein and drives the cell cycle for the cancer development and progression. CDK6 is also a substrate of ubiquitin; however, CDK6 SUMOylation at Lys 216 blocks its ubiquitination at Lys 147 and inhibits the ubiquitin-mediated CDK6 degradation. Throughout the cell cycle, CDK1 phosphorylates the SUMO-specific enzyme, ubiquitin-conjugating enzyme9 (UBC9) that in turn mediates CDK6 SUMOylation during mitosis; CDK6 remains SUMOylated in G1 phase and drives the cell cycle through G1/S transition. Thus, SUMO1–CDK6 conjugation constitutes a mechanism of cell cycle control and inhibition of this SUMOylation pathway may provide a strategy for treatment of glioblastoma.

Date: 2014
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DOI: 10.1038/ncomms5234

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