2. Academic Validation
  3. ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4

ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4

  • Nat Cell Biol. 2014 Jun;16(6):550-60. doi: 10.1038/ncb2959.
Sigrid B Thoresen 1,  Coen Campsteijn 1,  Marina Vietri 1,  Kay O Schink 1,  Knut Liestøl 2,  Jens S Andersen 3,  Camilla Raiborg 1,  Harald Stenmark 1
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
PMID: 24814515 DOI: 10.1038/ncb2959
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.

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