title: PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit.
abstract: Centrioles are duplicated and segregated in close link to the cell cycle. During mitosis, daughter centrioles are disengaged and eventually separated from mother centrioles. New daughter centrioles may be generated only after centriole separation. Therefore, centriole separation is considered a licensing step for centriole duplication. It was previously known that separase specifically cleaves pericentrin (PCNT) during mitotic exit. Here we report that PCNT has to be phosphorylated by PLK1 to be a suitable substrate of separase. Phospho-resistant mutants of PCNT are not cleaved by separase and eventually inhibit centriole separation. Furthermore, phospho-mimetic PCNT mutants rescue centriole separation even in the presence of a PLK1 inhibitor. On the basis on these results, we propose that PLK1 phosphorylation is a priming step for separase-mediated cleavage of PCNT and eventually for centriole separation. PLK1 phosphorylation of PCNT provides an additional layer of regulatory mechanism to ensure the fidelity of centriole separation during mitotic exit.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Jaeyoun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Kwanwoo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Kunsoo
authors.initials: K
authors.lastname: Rhee
mesh_terms: D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002502:Centrioles / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D064247:Separase / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000941:Antigens; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D064247:Separase; D000097869:Polo-Like Kinase 1; C086178:pericentrin