Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.

ABSTRACT: Proteins operate within dense interconnected networks, with interactions necessary both for stabilising proteins and enabling them to execute their molecular functions. Remarkably, protein-protein interaction networks operating within tumour cells continue to function despite widespread genetic perturbations. Previous work has demonstrated that tumour cells tolerate perturbations of paralogs better than perturbations of singleton genes, but the underlying mechanisms remain poorly understood. Here, we systematically profile the proteomic response of tumours and cell lines to gene loss. We find many examples of proteomic compensation, where loss of one gene causes increased abundance of a paralog, and collateral loss, where gene loss causes reduced paralog abundance. Compensation is enriched

SUBMITTER: Venkatesh A 

PROVIDER: S-EPMC12322171 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature