2. Academic Validation
  3. Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint

Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint

  • Cell Rep. 2018 Nov 27;25(9):2317-2328.e5. doi: 10.1016/j.celrep.2018.10.104.
Thomas Wild 1,  Magda Budzowska 2,  Susanne Hellmuth 3,  Susana Eibes 4,  Gopal Karemore 5,  Marin Barisic 6,  Olaf Stemmann 3,  Chunaram Choudhary 7
Affiliations

Affiliations

  • 1 Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • 2 Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Center for Chromosome Stability (CCS), Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • 3 Chair of Genetics, University of Bayreuth, Universitätsstraße 30, 95440 Bayreuth, Germany.
  • 4 Danish Cancer Society Research Center, Cell Division Laboratory, Strandboulevarden 49, 2100 Copenhagen, Denmark.
  • 5 Protein Imaging Platform, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • 6 Danish Cancer Society Research Center, Cell Division Laboratory, Strandboulevarden 49, 2100 Copenhagen, Denmark; Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 7 Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: chuna.choudhary@cpr.ku.dk.
PMID: 30485802 DOI: 10.1016/j.celrep.2018.10.104
Abstract

The multisubunit ubiquitin Ligase APC/C (anaphase-promoting complex/cyclosome) is essential for mitosis by promoting timely degradation of cyclin B1. APC/C is tightly regulated by the spindle assembly checkpoint (SAC), which involves Mps1 and MAD2-dependent temporal inhibition of APC/C. We analyzed the contribution of the APC/C subunits APC7 and APC16 to APC/C composition and function in human cells. APC16 is required for APC7 assembly into APC/C, whereas APC16 assembles independently of APC7. APC7 and APC16 knockout cells display no major defects in mitotic progression, cyclin B1 degradation, or SAC response, but APC/C lacking these two subunits shows reduced ubiquitylation activity in vitro. Strikingly, deletion of APC7 or APC16 is sufficient to provide synthetic viability to MAD2 deletion. ΔAPC7ΔMAD2 cells display accelerated mitosis and require SAC-independent Mps1 function for genome stability. These findings reveal that the composition of APC/C critically influences the importance of the SAC in humans.

Keywords

APC/C; APC16; APC7; MAD2; MPS1; mass spectrometry; mitosis; synthetic viability.

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