title: Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2.
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.
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Tianning
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.|Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Teng
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.|Center for Quantitative Biology, Peking University, Beijing 100871, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D030781:Organisms, Genetically Modified; D058105:Polymerization; D011485:Protein Binding; D034622:RNA Interference; D012441:Saccharomyces cerevisiae; D059008:Time-Lapse Imaging
chemical_list: C474610:CEP57 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C472643:Knl1 protein, human; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; C492664:MIS12 protein, human; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins