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Reference - PMID:12553909 - Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteasome.

Reference summary

PubMed ID
PMID:12553909
Title
Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteasome.
Authors
Yen HC, Gordon C, Chang EC
Citation
Cell 2003 Jan 24;112(2):207-17
Publication year
2003
Abstract
Yin6 is a yeast homolog of Int6, which is implicated in tumorigenesis. We show that Yin6 binds to and regulates proteasome activity. Overexpression of Yin6 strengthens proteasome function while inactivation weakens and causes the accumulation of polyubiquitinated proteins including securin/Cut2 and cyclin/Cdc13. Yin6 regulates the proteasome by preferentially interacting with Rpn5, a conserved proteasome subunit, and affecting its localization/assembly. We showed previously that Yin6 cooperates with Ras1 to mediate chromosome segregation; here, we demonstrate that Ras1 similarly regulates the proteasome via Rpn5. In yeast, human Int6 binds Rpn5 and regulates its localization. We propose that human Int6, either alone or cooperatively with Ras, influences proteasome activities via Rpn5. Inactivating Int6 can lead to accumulation of mitotic regulators affecting cell division and mitotic fidelity.

Annotation

Complementation

PBO:0003394 - functionally complemented by human INT6

Genes:

GO biological process

GO:0042307 - positive regulation of protein import into nucleus

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GO cellular component

GO:0005634 - nucleus

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GO:0000502 - proteasome complex

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GO molecular function

GO:0005515 - protein binding

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Multi-locus phenotype

FYPO:0000670 - abnormal mitotic sister chromatid separation

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Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

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Genotypes:

FYPO:0000838 - normal protein localization to nucleus during vegetative growth

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Single locus phenotype

FYPO:0000082 - decreased cell population growth at high temperature

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FYPO:0001407 - decreased cell population growth on glucose carbon source

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FYPO:0000846 - decreased protein degradation during vegetative growth

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FYPO:0004056 - decreased protein localization to nucleus, with protein mislocalized to cytoplasm

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FYPO:0002082 - increased protein ubiquitination during vegetative growth

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0001164 - normal growth on glucose carbon source

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FYPO:0002081 - normal growth on TPCK

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Genotypes:

FYPO:0001513 - normal mitotic sister chromatid segregation

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FYPO:0000833 - normal protein level during vegetative growth

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FYPO:0001357 - normal vegetative cell population growth

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FYPO:0000099 - sensitive to canavanine

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FYPO:0002080 - sensitive to TPCK

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Genotypes: