title: Cep68 can be regulated by Nek2 and SCF complex.
abstract: Centrosome cohesion maintains centrosomes in close proximity until mitosis, when cell cycle-dependent regulatory signaling events dissolve cohesion and promote centrosome separation in preparation for bipolar spindle assembly at mitosis. Cohesion is regulated by the antagonistic activities of the mitotic NIMA-related kinase 2 (Nek2), protein phosphatase 1, the cohesion fiber components rootletin, centrosomal Nek2-associated protein 1 (C-Nap1) and Cep68. The centrosomal protein Cep68 is essential for centrosome cohesion and dissociates from centrosomes at the onset of mitosis. Here, our cell line studies show the C-terminal 300-400 amino acids of Cep68 are necessary to localize Cep68 to interphase centrosomes while C-terminal 400-500 amino acids might regulate Cep68 dissociation from centrosomes at mitotic onset. In addition, Nek2 was demonstrated to phosphorylate Cep68 in vivo and this phosphorylation appears to promote Cep68 degradation in mitosis. We further show that the SCF complex destroys Cep68 at mitosis through recognition by the beta-Trcp F box component of SCF. Together, the findings provide a new insight into the control of centrosome separation by Cep68 during mitosis.
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117456, Singapore; Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Man
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Megraw
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117456, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Bioinformatics Institute, Agency for Science, Technology and Research, Singapore. Electronic address: bchlyp@nus.edu.sg.
authors.forename: Yoon Pin
authors.initials: YP
authors.lastname: Lim
mesh_terms: D018385:Centrosome / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008938:Mitosis; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*
chemical_list: C527270:CEP68 protein, human; D008869:Microtubule-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases
keywords: Cell cycle; Centrosome separation; Cep68; Nek2; SCF