Compartmentalized control of Cdk1 drives mitotic spindle assembly
| Autor: | Angela Flavia Serpico, Francesco Febbraro, Caterina Pisauro, Domenico Grieco |
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| Přispěvatelé: | Serpico, A. F., Febbraro, F., Pisauro, C., Grieco, D. |
| Rok vydání: | 2021 |
| Předmět: |
mitotic spindle assembly
Cdk1 QH301-705.5 Microtubule-associated protein Mitosis i-Cdk1 Spindle Apparatus HeLa Cell environment and public health General Biochemistry Genetics and Molecular Biology spindle assembly checkpoint Microtubule CDC2 Protein Kinase Wee1 Humans Biology (General) Kinase activity Phosphorylation Cytoskeleton Cyclin Cyclin-dependent kinase 1 Chemistry microtubule-associated proteins Mitosi compartmentalization microtubule-associated protein Cell biology Spindle apparatus enzymes and coenzymes (carbohydrates) MAP cell cycle biological phenomena cell phenomena and immunity Human HeLa Cells |
| Zdroj: | Cell Reports, Vol 38, Iss 4, Pp 110305-(2022) |
| ISSN: | 2211-1247 |
| Popis: | Summary: During cell division, dramatic microtubular rearrangements driven by cyclin B-cdk1 (Cdk1) kinase activity mark the onset of mitosis leading to dismantling of the interphase microtubular cytoskeleton and assembly of the mitotic spindle. During interphase, Cdk1 accumulates in an inactive state, phosphorylated at inhibitory sites by Wee1/Myt1 kinases. At mitosis onset, Cdc25 phosphatase dephosphorylates and activates Cdk1. Once activated, Cdk1 clears cytoplasmic microtubules by inhibiting microtubule-stabilizing and growth-promoting microtubule-associated proteins (MAPs). Nevertheless, some of these MAPs are required for spindle microtubule growth and spindle assembly, creating quite a conundrum. We show here that a Cdk1 fraction bound to spindle structures escapes Cdc25 action and remains inhibited by phosphorylation (i-Cdk1) in mitotic human cells. Loss or restoration of i-Cdk1 inhibits or promotes spindle assembly, respectively. Furthermore, polymerizing spindle microtubules foster i-Cdk1 aggregating with Wee1 and excluding Cdc25. Our data reveal that spindle assembly relies on compartmentalized control of Cdk1 activity. |
| Databáze: | OpenAIRE |
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