title: Characterization of Cep85 - a new antagonist of Nek2A that is involved in the regulation of centrosome disjunction.
abstract: Nek2 has been implicated in centrosome disjunction at the onset of mitosis to promote bipolar spindle formation, and hyperactivation of Nek2 leads to the premature centrosome separation. Its activity, therefore, needs to be strictly regulated. In this study, we report that Cep85, an uncharacterized centrosomal protein, acts as a binding partner of Nek2A. It colocalizes with isoform A of Nek2 (Nek2A) at centrosomes and forms a granule meshwork enveloping the proximal ends of centrioles. Opposite to the effects of Nek2A, overexpression of Cep85 in conjunction with inhibition of the motor protein Eg5 (also known as KIF11) leads to the failure of centrosome disjunction. By contrast, depletion of Cep85 results in the precocious centrosome separation. We also define the Nek2A binding and centrosome localization domains within Cep85. Although the Nek2A-binding domain alone is sufficient to inhibit Nek2A kinase activity in vitro, both domains are indispensable for full suppression of centrosome disjunction in cells. Thus, we propose that Cep85 is a bona fide Nek2A-binding partner that surrounds the proximal ends of centrioles where it cooperates with PP1γ (also known as PPP1CC) to antagonize Nek2A activity in order to maintain the centrosome integrity in interphase in mammalian cells.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China chench@xmu.edu.cn yuxw@xmu.edu.cn.
authors.forename: Canhe
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China chench@xmu.edu.cn yuxw@xmu.edu.cn.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D000072379:NIMA-Related Kinases; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C573619:CEP85L protein, human; D003598:Cytoskeletal Proteins; C470243:KIF11 protein, human; D015514:Oncogene Proteins, Fusion; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; C490317:Nek2 protein, mouse; D017346:Protein Serine-Threonine Kinases; C521052:Kif11 protein, mouse; D016547:Kinesins
keywords: Centrosome disjunction; Cep85; Nek2A