title: Proteasome activity is required for centromere separation independently of securin degradation in human cells.
abstract: Loss of centromere cohesion during anaphase in human cells is regulated by the spindle assembly checkpoint and is thought to depend on a ubiquitin ligase, the Anaphase Promoting Complex/Cyclosome (APC). APC-Cdc20 adds ubiquitin chains to securin inducing its destruction by the proteasome and these events correlate with the loss of sister chromatid cohesion and the onset of anaphase. But whether securin destruction is necessary and sufficient for anaphase initiation is not clear. Therefore, we asked if proteasome activity is needed for anaphase onset in human cells that lack securin. We find that even in the absence of securin, a metaphase block with cohered sister centromeres can be enforced in the absence of proteasome activity. Therefore, other targets of the proteasome must be degraded to allow anaphase onset.
authors.affiliation: Department of Genetics, Cell Biology & Development, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Giménez-Abián
authors.forename: Laura A
authors.initials: LA
authors.lastname: Díaz-Martínez
authors.forename: Karin G
authors.initials: KG
authors.lastname: Wirth
authors.forename: Consuelo
authors.initials: C
authors.lastname: De la Torre
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Clarke
mesh_terms: D000705:Anaphase / Q000502:physiology; D045744:Cell Line, Tumor; D002503:Centromere / Q000201:enzymology* / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D064249:Securin
chemical_list: D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D046988:Proteasome Endopeptidase Complex