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J Cell Biol. 2015 Nov 9;211(3):503-16. doi: 10.1083/jcb.201505114. Epub 2015 Nov 2.

TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.

Author information

1
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
2
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064 nbhalla@ucsc.edu.

Abstract

The spindle checkpoint acts during cell division to prevent aneuploidy, a hallmark of cancer. During checkpoint activation, Mad1 recruits Mad2 to kinetochores to generate a signal that delays anaphase onset. Yet, whether additional factors contribute to Mad2's kinetochore localization remains unclear. Here, we report that the conserved AAA+ ATPase TRIP13(PCH-2) localizes to unattached kinetochores and is required for spindle checkpoint activation in Caenorhabditis elegans. pch-2 mutants effectively localized Mad1 to unattached kinetochores, but Mad2 recruitment was significantly reduced. Furthermore, we show that the C. elegans orthologue of the Mad2 inhibitor p31(comet)(CMT-1) interacts with TRIP13(PCH-2) and is required for its localization to unattached kinetochores. These factors also genetically interact, as loss of p31(comet)(CMT-1) partially suppressed the requirement for TRIP13(PCH-2) in Mad2 localization and spindle checkpoint signaling. These data support a model in which the ability of TRIP13(PCH-2) to disassemble a p31(comet)/Mad2 complex, which has been well characterized in the context of checkpoint silencing, is also critical for spindle checkpoint activation.

PMID:
26527744
PMCID:
PMC4639874
DOI:
10.1083/jcb.201505114
[Indexed for MEDLINE]
Free PMC Article

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