title: Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing.
abstract: An intercentrosomal linker keeps a cell's two centrosomes joined together until it is dissolved at the onset of mitosis. A second connection keeps daughter centrioles engaged to their mothers until they lose their orthogonal arrangement at the end of mitosis. Centriole disengagement is required to license centrioles for duplication. We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP. We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. Cep68 and PCNT bind to different pools of Cep215. We propose that Cep68 degradation allows Cep215 removal from the peripheral PCM preventing centriole separation following disengagement, whereas PCNT cleavage mediates Cep215 removal from the core of the PCM to inhibit centriole disengagement and duplication.
authors.affiliation: Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York 10065, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Pagan
authors.affiliation: Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York 10065, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marzio
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York 10065, USA.
authors.forename: Mathew J K
authors.initials: MJ
authors.lastname: Jones
authors.affiliation: The Stowers Institute of Medical Research, 1000 East 50th Street, Kansas City Missouri 64110, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York 10065, USA.
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Jallepalli
authors.affiliation: The Stowers Institute of Medical Research, 1000 East 50th Street, Kansas City Missouri 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: 1] The Stowers Institute of Medical Research, 1000 East 50th Street, Kansas City Missouri 64110, USA [2] Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City Kansas 66160, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: 1] Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York 10065, USA [2] Howard Hughes Medical Institute, 522 First Avenue New York 10016, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
mesh_terms: D000941:Antigens / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002502:Centrioles / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008677:Metaphase / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D049468:Prometaphase / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D000097869:Polo-Like Kinase 1
chemical_list: D000941:Antigens; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D044843:SKP Cullin F-Box Protein Ligases; D000097869:Polo-Like Kinase 1; C405929:CDK5RAP2 protein, human; C527270:CEP68 protein, human; C086178:pericentrin