Kendrin Is a Novel Substrate for Separase Involved in the Licensing of Centriole Duplication

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 [1, 2]. Thus, centrosome duplication needs to be tig...

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Bibliographic Details
Published in:Current biology 2012-05, Vol.22 (10), p.915-921
Main Authors: Matsuo, Kazuhiko, Ohsumi, Keita, Iwabuchi, Mari, Kawamata, Toshio, Ono, Yoshitaka, Takahashi, Mikiko
Format: Article
Language:English
Subjects:
anaphase
Animals
Calmodulin-Binding Proteins - metabolism
carcinogenesis
Cell Cycle Proteins - metabolism
centrioles
Centrioles - physiology
Cercopithecus aethiops
chromatids
COS Cells
Endopeptidases - metabolism
HeLa Cells
Humans
mitosis
Mitosis - physiology
mutants
Separase
Xenopus
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Summary: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 [1, 2]. Thus, centrosome duplication needs to be tightly regulated to occur only once per cell cycle. Separase, a cysteine protease that triggers sister chromatid separation [3], is involved in centriole disengagement, which licenses centrosomes for the next round of duplication [4–8]. 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 [6, 7, 9, 10]. 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. ► Kendrin is directly cleaved by separase at a consensus site during mitosis ► The cleaved kendrin is released from centrosomes after a short lag ► Centriole disengagement coincides with a decrease in the kendrin signal ► Noncleavable kendrin expression suppresses centriole disengagement and duplication
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2012.03.048