RRC ID 45621
著者 Nelson CR, Hwang T, Chen PH, Bhalla N.
タイトル TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.
ジャーナル J Cell Biol
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.
巻・号 211(3)
ページ 503-16
公開日 2015-11-9
DOI 10.1083/jcb.201505114
PII jcb.201505114
PMID 26527744
PMC PMC4639874
MeSH Adaptor Proteins, Signal Transducing / metabolism Adenosine Triphosphatases / metabolism Animal Husbandry / methods Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism* Cell Cycle Checkpoints / physiology* Cell Cycle Proteins / metabolism* Kinetochores / metabolism* Mad2 Proteins / metabolism* Nuclear Proteins / metabolism Signal Transduction / physiology Spindle Apparatus / metabolism*
IF 8.811
引用数 18
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm1458