Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases (APTs). Live-cell analysis with DPPs reveals rapid growth-factor-mediated inhibition of the depalmitoylation activity of APTs, exposing a novel regulatory mechanism of dynamic lipid signaling.
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This work was supported by the University of Chicago, the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM119840) to B.C.D., the University of Chicago Medicine Comprehensive Cancer Center (P30CA14599), and a “Catalyst Award” to B.C.D. from the Chicago Biomedical Consortium, with support from the Searle Funds at The Chicago Community Trust. We thank J. Pu (University of Chicago) and D. Dammeier (University of Chicago) for technical assistance, and C. He (University of Chicago), A. Mukherje (National Institutes of Health), Y. Krishnan (University of Chicago), and J. Lewis (University of Chicago) for supplying materials and equipment.
The authors declare no competing financial interests.
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Kathayat, R., Elvira, P. & Dickinson, B. A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling. Nat Chem Biol 13, 150–152 (2017). https://doi.org/10.1038/nchembio.2262
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