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Sensors at Centrosomes Reveal Determinants of Local Separase Activity
Centriole disengagement in telophase/G1 is the licensing step for centrosome duplication in the subsequent S phase. Recent data suggest that separase, together with polo-like kinase Plk1, is essential for the centriole disengagement and individual depletion of either separase or Plk1 alone fails to suppress the centriole disengagement. This raises the question of how separase activity is regulated at the centrosome. By generating a series of separase sensors, we show that separase at centrosomes becomes active already in mid metaphase, well before its activity can be detected at the chromosomes. Depletion of the previously published inhibitors of centrosomal separase, astrin or Aki1, did not promote separase activity at the centrosomes. This indicates that morphological criteria like the formation of multipolar spindles are insufficient criteria upon which to base predictions about separase regulation. Finally, the ability of Plk1 to promote cleavage of the Scc1-based reporter but not of the kendrin reporter reveals regulation of separase activity at the substrate level. These results provide partial explanation of the role of Plk1 in centriole disengagement.
Vyšlo v časopise: Sensors at Centrosomes Reveal Determinants of Local Separase Activity. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004672
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004672Souhrn
Centriole disengagement in telophase/G1 is the licensing step for centrosome duplication in the subsequent S phase. Recent data suggest that separase, together with polo-like kinase Plk1, is essential for the centriole disengagement and individual depletion of either separase or Plk1 alone fails to suppress the centriole disengagement. This raises the question of how separase activity is regulated at the centrosome. By generating a series of separase sensors, we show that separase at centrosomes becomes active already in mid metaphase, well before its activity can be detected at the chromosomes. Depletion of the previously published inhibitors of centrosomal separase, astrin or Aki1, did not promote separase activity at the centrosomes. This indicates that morphological criteria like the formation of multipolar spindles are insufficient criteria upon which to base predictions about separase regulation. Finally, the ability of Plk1 to promote cleavage of the Scc1-based reporter but not of the kendrin reporter reveals regulation of separase activity at the substrate level. These results provide partial explanation of the role of Plk1 in centriole disengagement.
Zdroje
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Štítky
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