A fundamental requirement for growth of rapidly proliferating cells is metabolic adaptation to promote synthesis of biomass1. ATP citrate lyase (ACLY) is a critical enzyme responsible for synthesis of cytosolic acetyl-CoA, the key building component for de novo fatty acid synthesis and links vital pathways such as carbohydrate and lipid metabolism2. The mechanisms of ACLY regulation are not completely understood and the regulation of ACLY function by tyrosine phosphorylation is unknown... Our results reveal a novel mechanism for direct ACLY regulation that is subverted by multiple oncogenically-activated tyrosine kinases in diverse human cancers. These findings have significant implications for novel therapies targeting ACLY in cancer and metabolism. READ ARTICLE
BioRxiv DOI:10.1101/2020.01.20.910752
Authors: Johnvesly Basappa, Mahmoud A. ElAzzouny, Delphine C.M. Rolland, Anagh A. Sahasrabuddhe, Kaiyu Ma, Gleb A. Bazilevsky, Steven R. Hwang, Venkatesha Basrur, Kevin P. Conlon, Nathanael G. Bailey, John K. Frederiksen, Santiago Schnell, Yeqiao Zhou, David Cookmeyer, Jan M. Pawlicki, Amit Dipak Amin, James L. Riley, Robert B. Faryabi, Jonathan H Schatz, Kathryn E. Wellen, Ronen Marmorstein, Charles F. Burant, Kojo S.J. Elenitoba-Johnson, Megan S. Lim