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Plk1- and beta-TrCP-dependent degradation of Bora controls mitotic progression.

Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF-beta-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF-beta-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with beta-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression.

Pubmed ID: 18378770

Authors

  • Seki A
  • Coppinger JA
  • Du H
  • Jang CY
  • Yates JR
  • Fang G

Journal

The Journal of cell biology

Publication Data

April 7, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM062852
  • Agency: NHLBI NIH HHS, Id: HL079442
  • Agency: NHLBI NIH HHS, Id: R01 HL079442
  • Agency: NCRR NIH HHS, Id: RR11823-10

Mesh Terms

  • Amino Acid Motifs
  • Cell Cycle
  • Cell Cycle Proteins
  • HeLa Cells
  • Humans
  • Mitosis
  • Proteasome Endopeptidase Complex
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Ubiquitination
  • beta-Transducin Repeat-Containing Proteins