Abstract
Protein assembly is a highly dynamic process and proteins can interact in different ways and stoichiometries within a complex. The importance of maintaining protein stoichiometry for complex function and avoiding aggregation of orphan subunits has been demonstrated. However, how exactly the organization of proteins into complexes constrains differential protein abundance in extreme cellular conditions like cancer, where a lot of protein abundance changes occur, has not been systematically investigated. To study this, we collected proteomic data made available by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to quantify proteomic changes during carcinogenesis and systematically tested five interaction types in complexes to investigate which of these features impact on protein abundance correlation patterns in cancer. We found that higher than expected fraction of protein complex subunits does not show changes in their abundances compared to those in the normal samples. Furthermore, we found that the way proteins interact in complexes indeed constrains their co-abundance patterns. Our results highlight the role of the interactions between the proteins and the need of cancer cells to deal with aberrant changes in protein abundance.
Highlights
Cancer is a system that is characterized by a large number of somatic molecular alterations
Together these results suggest that protein-protein interactions (PPIs) and their organization into complexes limit the dysregulation of protein abundance; to which degree complex organization is important and how this buffering is achieved is poorly understood
We found a variation in the fraction of quantified proteins that showed significant abundant changes; 457 out of 6,554 proteins, 481 out of 6,478 proteins and 3,971 out of 10,316 proteins for COAD, hepatocellular carcinoma (HCC), and LUAD, respectively
Summary
Cancer is a system that is characterized by a large number of somatic molecular alterations. Many of these alterations appear on the level of the transcriptome and proteome of tumor cells. Multi-omics studies estimated that nearly 40% genes are under compensatory post-transcriptional control in response to CNAs (Sousa et al, 2019) Those buffered proteins are significantly enriched in protein complexes (Stingele et al, 2012; Gonçalves et al, 2017; Ishikawa et al, 2017; Ryan et al, 2017). Together these results suggest that protein-protein interactions (PPIs) and their organization into complexes limit the dysregulation of protein abundance; to which degree complex organization is important and how this buffering is achieved is poorly understood
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