Functional characterization of a positively charged specificity site in cyclin B1
| dc.contributor.author | Heinzle, Christian | |
| dc.date.accessioned | 2024-11-04T13:11:19Z | |
| dc.date.issued | 2024-11-04 | |
| dc.description.abstract | Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force of cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity is still poorly understood. Here, we discovered that a positively charged pocket in cyclin B1, which is exclusively conserved within B-type cyclins and binds phosphorylated serine- or threonine-residues, is essential for correct execution of mitosis. HeLa cells expressing pocket mutant cyclin B1 are strongly delayed in anaphase onset due to multiple defects in mitotic spindle function and timely activation of the E3 ligase APC/C. Pocket integrity is essential for APC/C phosphorylation particularly at non-consensus CDK1 sites and full in vitro ubiquitylation activity. Our results support a model in which cyclin B1’s pocket facilitates sequential substrate phosphorylations involving initial priming events that assist subsequent pocket-dependent phosphorylations even at non-consensus CDK1 motifs. | |
| dc.description.version | published | |
| dc.identifier.ppn | 1907482377 | |
| dc.identifier.uri | https://kops.uni-konstanz.de/handle/123456789/71108 | |
| dc.language.iso | eng | |
| dc.rights | terms-of-use | |
| dc.rights.uri | https://rightsstatements.org/page/InC/1.0/ | |
| dc.subject.ddc | 570 | |
| dc.title | Functional characterization of a positively charged specificity site in cyclin B1 | eng |
| dc.type | DOCTORAL_THESIS | |
| dspace.entity.type | Publication | |
| kops.citation.bibtex | @phdthesis{Heinzle2024-11-04Funct-71108,
year={2024},
title={Functional characterization of a positively charged specificity site in cyclin B1},
author={Heinzle, Christian},
address={Konstanz},
school={Universität Konstanz}
} | |
| kops.citation.iso690 | HEINZLE, Christian, 2024. Functional characterization of a positively charged specificity site in cyclin B1 [Dissertation]. Konstanz: Universität Konstanz | deu |
| kops.citation.iso690 | HEINZLE, Christian, 2024. Functional characterization of a positively charged specificity site in cyclin B1 [Dissertation]. Konstanz: University of Konstanz | eng |
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<dcterms:abstract>Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force of cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity is still poorly understood. Here, we discovered that a positively charged pocket in cyclin B1, which is exclusively conserved within B-type cyclins and binds phosphorylated serine- or threonine-residues, is essential for correct execution of mitosis. HeLa cells expressing pocket mutant cyclin B1 are strongly delayed in anaphase onset due to multiple defects in mitotic spindle function and timely activation of the E3 ligase APC/C. Pocket integrity is essential for APC/C phosphorylation particularly at non-consensus CDK1 sites and full in vitro ubiquitylation activity. Our results support a model in which cyclin B1’s pocket facilitates sequential substrate phosphorylations involving initial priming events that assist subsequent pocket-dependent phosphorylations even at non-consensus CDK1 motifs.</dcterms:abstract>
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| kops.date.examination | 2024-10-02 | |
| kops.date.yearDegreeGranted | 2024 | |
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| kops.identifier.nbn | urn:nbn:de:bsz:352-2-13dn7c1xtefz35 | |
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| temp.date.embargoEnd | 2026-11-04 |
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