Chromosomes undergo a major structural reorganization during mitosis. The first step in this reorganization is the compaction of interphase chromatin into highly condensed mitotic chromosomes. An evolutionarily conserved multi-subunit ATPase, the condensin complex, plays a critical role in establishing chromosome architecture and promoting chromosome condensation in mitosis. How does condensin promote chromosome condensation and how, in turn, is the cell cycle machinery activating or restraining condensin activity during the cell cycle are fundamental questions for cell biology. In this review, we examine the role of post-translational modifications, and in particular multi-site phosphorylation, in the regulation of condensin activity during the cell cycle. Remarkably, inspection of phosphorylation sites identified through multiple proteome-wide mass spectrometry analyses reveals that the phosphorylation landscape of condensin is highly conserved evolutionarily and that several kinases regulate condensin in vivo. This analysis leads us to propose a model, the ultrasensitive/kinase switch model, whereby the phosphorylation of condensin by multiple kinases allows the process of chromosome condensation to be maintained and even increased under fluctuating levels of cyclin-CDK activity during mitosis. Our model reconciles how chromosome condensation might be highly sensitive to low levels of CDK activity in early mitosis and subsequently insensitive to the declining levels of CDK activity in late mitosis.
机构:
Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Albuquerque, Claudio P.
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Smolka, Marcus B.
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机构:Univ Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Smolka, Marcus B.
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Payne, Samuel H.
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Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Payne, Samuel H.
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Bafna, Vineet
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Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Bafna, Vineet
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Eng, Jimmy
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Inst Syst Biol, Seattle, WA 98103 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Eng, Jimmy
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Zhou, Huilin
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Univ Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
机构:
Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Albuquerque, Claudio P.
;
Smolka, Marcus B.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Smolka, Marcus B.
;
Payne, Samuel H.
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h-index: 0
机构:
Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Payne, Samuel H.
;
Bafna, Vineet
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Bafna, Vineet
;
Eng, Jimmy
论文数: 0引用数: 0
h-index: 0
机构:
Inst Syst Biol, Seattle, WA 98103 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Eng, Jimmy
;
Zhou, Huilin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, Lab Prote Biol, CMM E, La Jolla, CA 92093 USA