Article ; Online: CDK activity at the centrosome regulates the cell cycle.
2024 Volume 43, Issue 4, Page(s) 114066
Abstract: In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due ...
Abstract | In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due to defective centrosomal localization or defective cyclin-substrate docking more widely is unknown. Here, we show that artificially restoring Cdc13-HPM centrosomal localization promotes mitotic entry and increases CDK (cyclin-dependent kinase) substrate phosphorylation at the centrosome and in the cytoplasm. We also show that the S-phase B-cyclin hydrophobic patch is required for centrosomal localization but not for S phase. We propose that the hydrophobic patch is essential for mitosis due to its requirement for the local concentration of cyclin-CDK with CDK substrates and regulators at the centrosome. Our findings emphasize the central importance of the centrosome as a hub coordinating cell-cycle control and explain why the cyclin hydrophobic patch is essential for mitosis. |
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MeSH term(s) | Centrosome/metabolism ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism ; Cyclin-Dependent Kinases/metabolism ; Cell Cycle ; Mitosis ; Phosphorylation ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/genetics ; Hydrophobic and Hydrophilic Interactions ; Humans ; Cyclin B |
Chemical Substances | Schizosaccharomyces pombe Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; Cdc13 protein, S pombe ; Cell Cycle Proteins ; Cyclin B |
Language | English |
Publishing date | 2024-04-04 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2649101-1 |
ISSN | 2211-1247 ; 2211-1247 |
ISSN (online) | 2211-1247 |
ISSN | 2211-1247 |
DOI | 10.1016/j.celrep.2024.114066 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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