title: ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4.
abstract: During the final stage of cell division, cytokinesis, the Aurora-B-dependent abscission checkpoint (NoCut) delays membrane abscission to avoid DNA damage and aneuploidy in cells with chromosome segregation defects. This arrest depends on Aurora-B-mediated phosphorylation of CHMP4C, a component of the endosomal sorting complex required for transport (ESCRT) machinery that mediates abscission, but the mechanism remains unknown. Here we describe ANCHR (Abscission/NoCut Checkpoint Regulator; ZFYVE19) as a key regulator of the abscission checkpoint, functioning through the most downstream component of the ESCRT machinery, the ATPase VPS4. In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing and prevent multinucleation in an Aurora-B-dependent manner. This association prevents VPS4 relocalization to the abscission zone and is relieved following inactivation of Aurora B to allow abscission. We propose that the abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring.
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Sigrid B
authors.initials: SB
authors.lastname: Thoresen
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Coen
authors.initials: C
authors.lastname: Campsteijn
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Marina
authors.initials: M
authors.lastname: Vietri
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Kay O
authors.initials: KO
authors.lastname: Schink
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Informatics, University of Oslo, N-0373 Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Raiborg
authors.affiliation: 1] Centre for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, Montebello, N-0379 Oslo, Norway [2] Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002843:Chromatin / Q000378:metabolism; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: C541008:CHMP4C protein, human; D002843:Chromatin; D056827:Endosomal Sorting Complexes Required for Transport; D008164:Luminescent Proteins; D015513:Oncogene Proteins; C472640:ZFYVE19 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human