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Reference - PMID:32361273 - Requirement of PP2A-B56 Par1 for the Stabilization of the CDK Inhibitor Rum1 and Activation of APC/C Ste9 during Pre-Start G1 in S. pombe.

Reference summary

PubMed ID
PMID:32361273
Title
Requirement of PP2A-B56 Par1 for the Stabilization of the CDK Inhibitor Rum1 and Activation of APC/C Ste9 during Pre-Start G1 in S. pombe.
Authors
Stonyte V, Martín R, Segura-Peña D, Sekulić N, Lopez-Aviles S
Citation
iScience 2020 May 22;23(5):101063
Publication year
2020
Abstract
Exit from the cell cycle during the establishment of quiescence and upon cell differentiation requires the sustained inactivation of CDK complexes. Fission yeast cells deprived of nitrogen halt cell cycle progression in pre-Start G1, before becoming quiescent or undergoing sexual differentiation. The CDK inhibitor Rum1 and the APC/C activator Ste9 are fundamental for this arrest, but both are down-regulated by CDK complexes. Here, we show that PP2A-B56 Par1 is instrumental for Rum1 stabilization and Ste9 activation. In the absence of PP2A-B56 Par1 , cells fail to accumulate Rum1, and this results in persistent CDK activity, Ste9 inactivation, retention of the mitotic cyclin Cdc13, and impaired withdrawal from the cell cycle during nitrogen starvation. Importantly, mutation of a putative B56 interacting motif in Rum1 recapitulates these defects. These results underscore the relevance of CDK-counteracting phosphatases in cell differentiation, establishment of the quiescent state, and escape from it in cancer cells.

Annotation

GO biological process

GO:0031568 - mitotic G1 cell size control checkpoint signaling

Genes:

GO:0007089 - traversing start control point of mitotic cell cycle

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GO molecular function

GO:0005515 - protein binding

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GO:0030674 - protein-macromolecule adaptor activity

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Modification

MOD:00696 - phosphorylated residue

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Multi-locus phenotype

FYPO:0007476 - decreased duration of cell cycle arrest in mitotic G1 phase

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Genotypes:

FYPO:0002798 - decreased protein degradation during nitrogen starvation

Genes:

Genotypes:

FYPO:0001283 - decreased protein level during cellular response to nitrogen starvation

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FYPO:0000998 - elongated cell during nitrogen starvation

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FYPO:0001043 - increased mating efficiency

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Genotypes:

FYPO:0002277 - increased protein degradation during nitrogen starvation

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FYPO:0001387 - loss of viability at high temperature

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Genotypes:

FYPO:0001000 - normal cell cycle arrest in mitotic G1 phase during nitrogen starvation

Genes:

Genotypes:

FYPO:0002801 - normal protein degradation during nitrogen starvation

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Genotypes:

FYPO:0006822 - viable small vegetative cell with normal cell growth rate

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Single locus phenotype

FYPO:0003345 - abolished cell cycle arrest in mitotic G1 phase in response to nitrogen starvation

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Genotypes:

FYPO:0004233 - decreased and delayed cell cycle arrest in mitotic G1 phase in response to nitrogen starvation

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Genotypes:

FYPO:0000708 - decreased mating efficiency

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Genotypes:

FYPO:0002798 - decreased protein degradation during nitrogen starvation

Genes:

Genotypes:

FYPO:0005034 - decreased protein phosphorylation during nitrogen starvation

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Genotypes:

FYPO:0001645 - decreased protein-protein interaction

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Genotypes:

FYPO:0001152 - decreased RNA level during nitrogen starvation

Genes:

Genotypes:

FYPO:0001043 - increased mating efficiency

Genes:

Genotypes:

FYPO:0002277 - increased protein degradation during nitrogen starvation

Genes:

Genotypes:

FYPO:0002681 - increased protein phosphorylation during nitrogen starvation

Genes:

Genotypes:

FYPO:0004084 - normal protein level during nitrogen starvation

Genes:

Genotypes:

FYPO:0005035 - normal protein phosphorylation during nitrogen starvation

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Genotypes: