Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis.

ABSTRACT: It has been a consensus in cancer research that cancer is a disease caused primarily by genomic alterations, especially somatic mutations. However, the mechanism of mutation-induced oncogenesis is not fully understood. Here, we used the mitochondrial apoptotic pathway as a case study and performed a systematic analysis of integrating pathway dynamics with protein interaction kinetics to quantitatively investigate the causal molecular mechanism of mutation-induced oncogenesis. A mathematical model of the regulatory network was constructed to establish the functional role of dynamic bifurcation in the apoptotic process. The oncogenic mutation enrichment of each of the protein functional domains involved was found strongly correlated with the parameter sensitivity of the bifurcation point. We

SUBMITTER: Zhao L 

PROVIDER: S-EPMC4522770 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature