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

Anita Bellail, Jeffrey J. Olson, Chunhai Hao

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Article number4234
JournalNature Communications
Volume5
DOIs
StatePublished - Jun 23 2014
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase 6
Sumoylation
Glioblastoma
Ubiquitin
progressions
Cell Cycle
Cells
proteins
cycles
Cyclin-Dependent Kinases
Ubiquitination
Ubiquitin-Conjugating Enzymes
Cell Cycle Proteins
Cyclins
G1 Phase
Degradation
Cell Cycle Checkpoints
Mitosis
degradation
mitosis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. / Bellail, Anita; Olson, Jeffrey J.; Hao, Chunhai.

In: Nature Communications, Vol. 5, 4234, 23.06.2014.

Research output: Contribution to journalArticle

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