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

Sasha A. Singh, Dominic Winter, Marc Kirchner, Ruchi Chauhan, Saima Ahmed, Nurhan Ozlu, Amit Tzur, Judith A. Steen, Hanno Steen

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Using multiplexed quantitative proteomics, we analyzed cell cycledependent 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/CCDH1- 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.

Original languageEnglish
Pages (from-to)385-399
Number of pages15
JournalEMBO Journal
Issue number4
StatePublished - 18 Feb 2014


  • Dynamic proteomics
  • Protein profile similarity screening
  • Quantitative proteomics
  • TMT-labeling
  • Ubiquitination-dependent protein degradation


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