Identification of Genes and Pathways Linking Cancer Metabolism to Cell Surface Dynamics through Protein N-glycosylation
Year: 2014
Type: dissertation
Abstract: N-glycosylation is a co-translational modification that covalently attaches oligosaccharide to and regulates proper folding, trafficking, and surface residency of secreted proteins. MGAT5 encodes a glycosyltransferase that synthesizes β1,6GlcNAc-branched N-glycans in medial Golgi. MGAT5 is frequently up-regulated in and associated with the progression of multiple types of human carcinomas. In order to identify Mgat5 interacting genes and signaling pathways, immortalized mouse embryonic fibroblast (MEF) cell lines that are Mgat5 wild-type and null were established on p53 null genetic background. Pooled lentiviral shRNA drop-out screens revealed that mTOR pathway was essential in the wild-type MEFs, whereas signaling dependency shifts to RAS-MEK-ERK pathway was observed in the null cells. Metabolite profiling of the MEFs and human cell lines with MGAT5 knock-down showed drastic changes in tricarboxylic acid cycle metabolites and amino acids upon MGAT5 disruption. Together, these approaches permitted a global survey of genetic and metabolic changes that occur when MGAT5 is disturbed.
Source: TSpace (University of Toronto)
Author: Xiangyuan Ma
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2620979993