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Reference - PMID:24055157 - CK1 is required for a mitotic checkpoint that delays cytokinesis.

Reference summary

PubMed ID
PMID:24055157
Title
CK1 is required for a mitotic checkpoint that delays cytokinesis.
Authors
Johnson AE, Chen JS, Gould KL
Citation
Curr Biol 2013 Oct 07;23(19):1920-6
Publication year
2013
Abstract
Failure to accurately partition genetic material during cell division causes aneuploidy and drives tumorigenesis. Cell-cycle checkpoints safeguard cells from such catastrophes by impeding cell-cycle progression when mistakes arise. FHA-RING E3 ligases, including human RNF8 and CHFR and fission yeast Dma1, relay checkpoint signals by binding phosphorylated proteins via their FHA domains and promoting ubiquitination of downstream targets. Upon mitotic checkpoint activation, S. pombe Dma1 concentrates at spindle pole bodies (SPBs) in an FHA-dependent manner and ubiquitinates Sid4, a scaffold of Polo kinase, to suspend cytokinesis. However, the kinase or kinases that phosphoprime Sid4 for Dma1-mediated ubiquitination are unknown. Here, we report that the highly conserved protein kinase CK1 transmits the signal necessary to stall cytokinesis by phosphopriming Sid4 for Dma1-mediated ubiquitination. Like Dma1, CK1 accumulates at SPBs during a mitotic arrest and associates stably with SPB components, including Sid4. Our results establish CK1 as an integral component of a mitotic, ubiquitin-mediated checkpoint pathway.

Annotation

GO biological process

GO:0032466 - negative regulation of cytokinesis

Genes:

GO:0031030 - negative regulation of septation initiation signaling

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GO cellular component

GO:0032153 - cell division site

Genes:

GO:0005634 - nucleus

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GO:0005816 - spindle pole body

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GO molecular function

GO:0004674 - protein serine/threonine kinase activity

Genes:

GO:0035591 - signaling adaptor activity

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Modification

MOD:00696 - phosphorylated residue

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Multi-locus phenotype

FYPO:0000941 - abolished protein localization to mitotic spindle pole body

Genes:

Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

Single locus phenotype

FYPO:0000912 - abolished protein ubiquitination during vegetative growth

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0004537 - mitotic spindle assembly checkpoint override

Genes:

Genotypes:

FYPO:0002967 - normal protein localization to mitotic spindle pole body

Genes:

Genotypes:

FYPO:0002635 - normal protein ubiquitination during vegetative growth

Genes:

Genotypes: