Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26743940.
- Also identified by DOI 10.1038/ncomms10151 and PMC identifier 4729865.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1-Mad2 is crucial for SAC activation. However, the mechanism by which Mad1-Mad2 accumulation at kinetochores is regulated is not clear. Here we find that Cep57 is localized to kinetochores in human cells, and binds to Mis12, a KMN (KNL1/Mis12 complex/Ndc80 complex) network component. Cep57 also interacts with Mad1, and depletion of Cep57 results in decreased kinetochore localization of Mad1-Mad2, reduced SAC signalling and increased chromosome segregation errors. We also show that the microtubule-binding activity of Cep57 is involved in the timely removal of Mad1 from kinetochores. Thus, these findings reveal that the KMN network-binding protein Cep57 is a mitotic kinetochore component, and demonstrate the functional connection between the KMN network and the SAC.
Medical subject headings
- Cell Cycle Proteins
- Kinetochores
- M Phase Cell Cycle Checkpoints
- Mad2 Proteins
- Microtubule-Associated Proteins
- Microtubules
- Nuclear Proteins