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.
Seki
Akiko
A
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Coppinger
Judith A
JA
Du
Haining
H
Jang
Chang-Young
CY
Yates
John R
JR
Fang
Guowei
G
D020816:Amino Acid Motifs; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D054875:Ubiquitination; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D000097869:Polo-Like Kinase 1; C471644:BTRC protein, human; C528235:bora protein, human