Title: Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A
Authors: Leaver, DJ
Cleary, B
Nguyen, N
Priebbenow, DL
Lagiakos, HR
Sanchez, J
Xue, L
Huang, F
Sun, YX
Mujumdar, P
Mudududdla, R
Varghese, S
Teguh, S
Charman, SA
White, KL
Katneni, K
Cuellar, M
Strasser, JM
Dahlin, JL
Walters, MA
Street, IP
Monahan, BJ
Jarman, KE
Sabroux, HJ
Falk, H
Chung, MC
Hermans, SJ
Parker, MW
Thomas, T
Baell, JB
Issue Year: 2019
Publisher AMER CHEMICAL SOC
Series JOURNAL OF MEDICINAL CHEMISTRY:
Abstract Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry-based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross-species phosphosite responses, as well as unique model-specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK-mediated phosphorylation of STIM1 negatively regulates store-operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross-species resource of exercise-regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux.
URI: https://publications.svi.edu.au/publications/7721
Other Identifiers 10.1021/acs.jmedchem.9b00665
Publication type Article