Analog-sensitive Cdk1 as a tool to study mitotic exit: protein phosphatase 1 is required downstream from Cdk1 inactivation in budding yeast.


Journal

Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology
ISSN: 1573-6849
Titre abrégé: Chromosome Res
Pays: Netherlands
ID NLM: 9313452

Informations de publication

Date de publication:
10 09 2023
Historique:
received: 06 04 2023
accepted: 23 08 2023
revised: 17 08 2023
medline: 12 9 2023
pubmed: 10 9 2023
entrez: 10 9 2023
Statut: epublish

Résumé

We show that specific inactivation of the protein kinase Cdk1/cyclin B (Cdc28/Clb2) triggers exit from mitosis in the budding yeast Saccharomyces cerevisiae. Cells carrying the allele cdc28-as1, which makes Cdk1 (Cdc28) uniquely sensitive to the ATP analog 1NM-PP1, were arrested with spindle poisons and then treated with 1NM-PP1 to inhibit Cdk1. This caused the cells to leave mitosis and enter G1-phase as shown by initiation of rebudding (without cytokinesis), induction of mating projections ("shmoos") by α-factor, stabilization of Sic1, and degradation of Clb2. It is known that Cdk1 must be inactivated for cells to exit mitosis, but our results show that inactivation of Cdk1 is not only necessary but also sufficient to initiate the transition from mitosis to G1-phase. This result suggests a system in which to test requirements for particular gene products downstream from Cdk1 inactivation, for example, by combining cdc28-as1 with conditional mutations in the genes of interest. Using this approach, we demonstrate that protein phosphatase 1 (PPase1; Glc7 in S. cerevisiae) is required for mitotic exit and reestablishment of interphase following Cdk1 inactivation. This system could be used to test the need for other protein phosphatases downstream from Cdk1 inactivation, such as PPase 2A and Cdc14, and it could be combined with phosphoproteomics to gain information about the substrates that the various phosphatases act upon during mitotic exit.

Identifiants

pubmed: 37690059
doi: 10.1007/s10577-023-09736-6
pii: 10.1007/s10577-023-09736-6
doi:

Substances chimiques

Protein Phosphatase 1 EC 3.1.3.16
CDC28 Protein Kinase, S cerevisiae EC 2.7.11.22
GLC7 protein, S cerevisiae EC 3.1.3.16

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

27

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature B.V.

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Auteurs

Jason M Keaton (JM)

Acacia Safety Consulting, Inc, P.O. Box 342603, Milwaukee, WI, 53234, USA.
Department of Chemistry, University of Wisconsin-Oshkosh, Oshkosh, WI, 54901, USA.

Benjamin G Workman (BG)

Department of Chemistry, University of Wisconsin-Oshkosh, Oshkosh, WI, 54901, USA.

Linfeng Xie (L)

Department of Chemistry, University of Wisconsin-Oshkosh, Oshkosh, WI, 54901, USA.

James R Paulson (JR)

Department of Chemistry, University of Wisconsin-Oshkosh, Oshkosh, WI, 54901, USA. paulson@uwosh.edu.

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