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. Epub 2014 May 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism*
  • Cell Cycle Checkpoints*
  • Chromatin / metabolism
  • Chromosome Aberrations
  • Chromosome Segregation
  • Cytokinesis*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phosphorylation
  • Protein Transport
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism*


  • CHMP4C protein, human
  • Chromatin
  • Endosomal Sorting Complexes Required for Transport
  • Luminescent Proteins
  • Oncogene Proteins
  • ZFYVE19 protein, human
  • AURKB protein, human
  • Aurora Kinase B
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities
  • VPS4A protein, human