title: Kendrin is a novel substrate for separase involved in the licensing of centriole duplication.
abstract: The centrosome, consisting of a pair of centrioles surrounded by pericentriolar material, directs the formation of bipolar spindles during mitosis. Aberrant centrosome number can promote chromosome instability, which is implicated in tumorigenesis. Thus, centrosome duplication needs to be tightly regulated to occur only once per cell cycle. Separase, a cysteine protease that triggers sister chromatid separation, is involved in centriole disengagement, which licenses centrosomes for the next round of duplication. However, at least two questions remain unsolved: what is the substrate relevant to the disengagement, and how does separase, activated at anaphase onset, act on the disengagement that occurs during late mitosis. Here, we show that kendrin, also named pericentrin, is cleaved by activated separase at a consensus site in vivo and in vitro, and this leads to the delayed release of kendrin from the centrosome later in mitosis. Furthermore, we demonstrate that expression of a noncleavable kendrin mutant suppresses centriole disengagement and subsequent centriole duplication. Based on these results, we propose that kendrin is a novel and crucial substrate for separase at the centrosome, protecting the engaged centrioles from premature disengagement and thereby blocking reduplication until the cell passes through mitosis.
authors.affiliation: Faculty of Pharmaceutical Science, Teikyo Heisei University, Ichihara, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuo
authors.forename: Keita
authors.initials: K
authors.lastname: Ohsumi
authors.forename: Mari
authors.initials: M
authors.lastname: Iwabuchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kawamata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ono
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D019556:COS Cells; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000502:physiology*; D002522:Chlorocebus aethiops; D010450:Endopeptidases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D064247:Separase; D014981:Xenopus
chemical_list: D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins; C410004:kendrin; D010450:Endopeptidases; C577987:ESPL1 protein, human; D064247:Separase