Open AccessInteractome disassembly during apoptosis occurs independent of caspase cleavage
Author(s) -
Scott Nichollas E,
Rogers Lindsay D,
Prudova Anna,
Brown Nat F,
Fortelny Nikolaus,
Overall Christopher M,
Foster Leonard J
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20167067
Subject(s) - interactome , biology , microbiology and biotechnology , proteome , proteomics , apoptosis , caspase , quantitative proteomics , caspase 7 , proteolysis , protein–protein interaction , caspase 2 , programmed cell death , computational biology , bioinformatics , biochemistry , gene , enzyme
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.