title: Anaphase specific auto-cleavage of separase.
abstract: Sister-chromatid separation is triggered by a specific proteolytic cleavage of chromosomal cohesins catalyzed by the endopeptidase separase. Prior to anaphase, separase is inhibited independently by affinity binding to securin and by specific inhibitory phosphorylation. Here we show that separase itself is also subjected to proteolytic cleavages at three adjacent sites. The cleavages are auto-catalyzed and occur specifically at anaphase coincident with separase activation. The cleaved fragments remain associated with each other and are catalytically active. Mapping of the cleavage sites reveals that all three sites are conserved in vertebrates underlining a significant function for this regulation.
authors.affiliation: Department of Molecular Biology, UT Southwestern Medical Center at Dallas, 75390, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.forename: Olaf
authors.initials: O
authors.lastname: Stemman
authors.forename: Jens S
authors.initials: JS
authors.lastname: Anderson
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002842:Chromatids / Q000502:physiology; D017124:Conserved Sequence; D010450:Endopeptidases; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009068:Movement / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064247:Separase; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D010450:Endopeptidases; C577987:ESPL1 protein, human; D064247:Separase