Interactome disassembly during apoptosis occurs independent of caspase cleavage

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Author
Scott, NE; Rogers, LD; Prudova, A; Brown, NF; Fortelny, N; Overall, CM; Foster, LJDate
2017-01-01Source Title
Molecular Systems BiologyPublisher
WILEYUniversity of Melbourne Author/s
Scott, NichollasAffiliation
Microbiology and ImmunologyMetadata
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Journal ArticleCitations
Scott, N. E., Rogers, L. D., Prudova, A., Brown, N. F., Fortelny, N., Overall, C. M. & Foster, L. J. (2017). Interactome disassembly during apoptosis occurs independent of caspase cleavage. MOLECULAR SYSTEMS BIOLOGY, 13 (1), https://doi.org/10.15252/msb.20167067.Access Status
Open AccessAbstract
Protein-protein interaction networks (interactomes) define the functionality of all biological systems. In apoptosis, proteolysis by caspases is thought to initiate disassembly of protein complexes and cell death. Here we used a quantitative proteomics approach, protein correlation profiling (PCP), to explore changes in cytoplasmic and mitochondrial interactomes in response to apoptosis initiation as a function of caspase activity. We measured the response to initiation of Fas-mediated apoptosis in 17,991 interactions among 2,779 proteins, comprising the largest dynamic interactome to date. The majority of interactions were unaffected early in apoptosis, but multiple complexes containing known caspase targets were disassembled. Nonetheless, proteome-wide analysis of proteolytic processing by terminal amine isotopic labeling of substrates (TAILS) revealed little correlation between proteolytic and interactome changes. Our findings show that, in apoptosis, significant interactome alterations occur before and independently of caspase activity. Thus, apoptosis initiation includes a tight program of interactome rearrangement, leading to disassembly of relatively few, select complexes. These early interactome alterations occur independently of cleavage of these protein by caspases.
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