Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle
Summary: A series of sequential events orchestrates cell growth and division, set in motion by cyclin-dependent kinases (Cdks). In the “qualitative model” for Cdk control, order is achieved by cell cycle stage-specific cyclins. However, single-cyclin cells retain cell cycle order. In an alternative...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003055 |
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| author | Luca Takacs Lina Gerontogianni Kimberly Quililan Helen Flynn Frank Uhlmann |
| author_facet | Luca Takacs Lina Gerontogianni Kimberly Quililan Helen Flynn Frank Uhlmann |
| author_sort | Luca Takacs |
| collection | DOAJ |
| description | Summary: A series of sequential events orchestrates cell growth and division, set in motion by cyclin-dependent kinases (Cdks). In the “qualitative model” for Cdk control, order is achieved by cell cycle stage-specific cyclins. However, single-cyclin cells retain cell cycle order. In an alternative “quantitative model,” increasing Cdk activity triggers substrate phosphorylation at sequential thresholds. Here, we test a key prediction from the quantitative model: the best Cdk substrates should be the first to be phosphorylated. Phosphoproteome analysis of synchronous budding yeast cultures, against expectations, reveals little correlation between known in vitro Cdk phosphorylation rates and observed in vivo phosphorylation timing. Incorporating Cdk-counteracting phosphatases that impose phosphorylation thresholds does not improve the correlation. Instead of kinase-phosphatase control (i.e., “regulator control”), our phosphoproteome patterns reveal signatures of “substrate control,” including substrate-defined phosphorylation waves. The changing behavior of the substrates themselves therefore contributes to ordering their Cdk phosphorylation during the budding yeast cell cycle. |
| format | Article |
| id | doaj-art-e5763aeec63e44b68bc1269688aabb9b |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-e5763aeec63e44b68bc1269688aabb9b2025-08-20T02:16:02ZengElsevierCell Reports2211-12472025-04-0144411553410.1016/j.celrep.2025.115534Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycleLuca Takacs0Lina Gerontogianni1Kimberly Quililan2Helen Flynn3Frank Uhlmann4Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UKBioinformatics & Biostatistics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UKChromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UKProteomics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UKChromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Corresponding authorSummary: A series of sequential events orchestrates cell growth and division, set in motion by cyclin-dependent kinases (Cdks). In the “qualitative model” for Cdk control, order is achieved by cell cycle stage-specific cyclins. However, single-cyclin cells retain cell cycle order. In an alternative “quantitative model,” increasing Cdk activity triggers substrate phosphorylation at sequential thresholds. Here, we test a key prediction from the quantitative model: the best Cdk substrates should be the first to be phosphorylated. Phosphoproteome analysis of synchronous budding yeast cultures, against expectations, reveals little correlation between known in vitro Cdk phosphorylation rates and observed in vivo phosphorylation timing. Incorporating Cdk-counteracting phosphatases that impose phosphorylation thresholds does not improve the correlation. Instead of kinase-phosphatase control (i.e., “regulator control”), our phosphoproteome patterns reveal signatures of “substrate control,” including substrate-defined phosphorylation waves. The changing behavior of the substrates themselves therefore contributes to ordering their Cdk phosphorylation during the budding yeast cell cycle.http://www.sciencedirect.com/science/article/pii/S2211124725003055CP: Cell biologyCP: Molecular biology |
| spellingShingle | Luca Takacs Lina Gerontogianni Kimberly Quililan Helen Flynn Frank Uhlmann Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle Cell Reports CP: Cell biology CP: Molecular biology |
| title | Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle |
| title_full | Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle |
| title_fullStr | Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle |
| title_full_unstemmed | Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle |
| title_short | Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle |
| title_sort | evidence of substrate control of cdk phosphorylation during the budding yeast cell cycle |
| topic | CP: Cell biology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003055 |
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