Interactome Rewiring Through Cancer-associated Mutation in Growth Factor Signaling Pathways
Year: 2017
Type: dissertation
Abstract: Many somatic mutations acquired in cancer have been identified in upstream regulators that normally relay growth factor signals to downstream effectors, notably kinases (PI3 kinase, AKT, RAF), phosphatases (PTEN) and G-proteins (K-Ras). This work seeks to apply both affinity purification coupled to MS (AP-MS) and BioID to quantitatively characterize changes in protein interactions between wild-type (wt) and cancer-associated mutations. In this study, 26 wt proteins and 27 cancer-associated mutants were profiled using both AP-MS and BioID. Several novel interactions and multiple differential associations were revealed. I validated that mutant Raf-1 and A-Raf display increased interactions with subunits of protein phosphatase 6, which may impact the activation of the classical Raf-ERK pathway and the Hippo pathway. The results presented in this thesis show that interaction profiles are often altered in cancer-associated mutants in growth factor pathways, identifying many routes of potential crosstalk with the Hippo pathway, HER2 signaling, and translation initiation.
Source: TSpace (University of Toronto)
Author: Cassandra-Jin Wong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3143792447