Positively charged specificity site in cyclin B1 is essential for mitotic fidelity DOI Creative Commons
Thomas U. Mayer,

Christian Heinzle,

Anna Höfler

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 9, 2024

Abstract Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity still poorly understood. Here, we discovered that a positively charged pocket in cyclin B1, which exclusively conserved within B-type and binds phosphorylated serine- or threonine-residues, essential for correct execution mitosis. HeLa cells expressing mutant B1 strongly delayed anaphase onset due multiple defects mitotic spindle function timely activation E3 ligase APC/C. Pocket integrity APC/C phosphorylation particularly at non-consensus CDK1 sites full vitro ubiquitylation activity. Our results support model B1’s serves as site factor sequential phosphorylations involving initial priming events facilitate subsequent pocket-dependent even motifs.

Язык: Английский

Positively charged specificity site in cyclin B1 is essential for mitotic fidelity DOI Creative Commons
Thomas U. Mayer,

Christian Heinzle,

Anna Höfler

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 9, 2024

Abstract Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity still poorly understood. Here, we discovered that a positively charged pocket in cyclin B1, which exclusively conserved within B-type and binds phosphorylated serine- or threonine-residues, essential for correct execution mitosis. HeLa cells expressing mutant B1 strongly delayed anaphase onset due multiple defects mitotic spindle function timely activation E3 ligase APC/C. Pocket integrity APC/C phosphorylation particularly at non-consensus CDK1 sites full vitro ubiquitylation activity. Our results support model B1’s serves as site factor sequential phosphorylations involving initial priming events facilitate subsequent pocket-dependent even motifs.

Язык: Английский

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