@article{6dc4914dd6744c7d927219c5e981a73c,
title = "Co-regulation proteomics reveals substrates and mechanisms of APC/C-dependent degradation",
abstract = "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.",
keywords = "Dynamic proteomics, Protein profile similarity screening, Quantitative proteomics, TMT-labeling, Ubiquitination-dependent protein degradation",
author = "Singh, \{Sasha A.\} and Dominic Winter and Marc Kirchner and Ruchi Chauhan and Saima Ahmed and Nurhan Ozlu and Amit Tzur and Steen, \{Judith A.\} and Hanno Steen",
year = "2014",
month = feb,
day = "18",
doi = "10.1002/embj.201385876",
language = "אנגלית",
volume = "33",
pages = "385--399",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "4",
}