title: Global Profiling of Acetyltransferase Feedback Regulation.
abstract: Lysine acetyltransferases (KATs) are key mediators of cell signaling. Methods capable of providing new insights into their regulation thus constitute an important goal. Here we report an optimized platform for profiling KAT-ligand interactions in complex proteomes using inhibitor-functionalized capture resins. This approach greatly expands the scope of KATs, KAT complexes, and CoA-dependent enzymes accessible to chemoproteomic methods. This enhanced profiling platform is then applied in the most comprehensive analysis to date of KAT inhibition by the feedback metabolite CoA. Our studies reveal that members of the KAT superfamily possess a spectrum of sensitivity to CoA and highlight NAT10 as a novel KAT that may be susceptible to metabolic feedback inhibition. This platform provides a powerful tool to define the potency and selectivity of reversible stimuli, such as small molecules and metabolites, that regulate KAT-dependent signaling.
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Montgomery
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Garlick
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.
authors.forename: Rhushikesh A
authors.initials: RA
authors.lastname: Kulkarni
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Ontario MG5 1L7, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Ontario MG5 1L7, Canada.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Allali-Hassani
authors.affiliation: Fox Chase Cancer Institute , Philadelphia, Pennsylvania 19111, United States.
authors.forename: Yin-Ming
authors.initials: YM
authors.lastname: Kuo
authors.affiliation: Fox Chase Cancer Institute , Philadelphia, Pennsylvania 19111, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Andrews
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Ontario MG5 1L7, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Ontario MG5 1L7, Canada.
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.|Department of Pharmacology and Toxicology, University of Toronto , Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Meier
mesh_terms: D002384:Catalysis; D002853:Chromatography, Liquid; D003065:Coenzyme A / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000070837:Lysine Acetyltransferases / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D000070837:Lysine Acetyltransferases; D003065:Coenzyme A