RT Journal Article
SR Electronic
T1 Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 149716
DO 10.1101/149716
A1 Emanuel Gonçalves
A1 Marco Sciacovelli
A1 Ana S. H. Costa
A1 Timothy Isaac Johnson
A1 Daniel Machado
A1 Christian Frezza
A1 Julio Saez-Rodriguez
YR 2017
UL http://biorxiv.org/content/early/2017/06/13/149716.abstract
AB Deregulated signal transduction pathways and energy metabolism are hallmarks of cancer and both play a fundamental role in the process of tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we show that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers.