Co-regulation proteomics reveals substrates and mechanisms of APC/C-dependent degradation

EMBO J. 2014 Feb 18;33(4):385-99. doi: 10.1002/embj.201385876. Epub 2014 Feb 6.


Using multiplexed quantitative proteomics, we analyzed cell cycle-dependent changes of the human proteome. We identified >4,400 proteins, each with a six-point abundance profile across the cell cycle. Hypothesizing that proteins with similar abundance profiles are co-regulated, we clustered the proteins with abundance profiles most similar to known Anaphase-Promoting Complex/Cyclosome (APC/C) substrates to identify additional putative APC/C substrates. This protein profile similarity screening (PPSS) analysis resulted in a shortlist enriched in kinases and kinesins. Biochemical studies on the kinesins confirmed KIFC1, KIF18A, KIF2C, and KIF4A as APC/C substrates. Furthermore, we showed that the APC/C(CDH1)-dependent degradation of KIFC1 regulates the bipolar spindle formation and proper cell division. A targeted quantitative proteomics experiment showed that KIFC1 degradation is modulated by a stabilizing CDK1-dependent phosphorylation site within the degradation motif of KIFC1. The regulation of KIFC1 (de-)phosphorylation and degradation provides insights into the fidelity and proper ordering of substrate degradation by the APC/C during mitosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cell Cycle
  • HeLa Cells
  • Humans
  • Kinesins / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Proteolysis*
  • Proteomics*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Ubiquitination


  • KIFC1 protein, human
  • Recombinant Fusion Proteins
  • Anaphase-Promoting Complex-Cyclosome
  • KIF18A protein, human
  • Kinesins