Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
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Thinon E, Serwa RA, Broncel M, Brannigan JA, Brassat U, Wright MH, Heal WP, Wilkinson AJ, Mann DJ, Tate EW
Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
Nat Commun. 2014 Sep 26;5:4919. doi: 10.1038/ncomms5919.
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25255805 [View in PubMed]
- Abstract
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Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells.
DrugBank Data that Cites this Article
- Polypeptides
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Name UniProt ID NADH-cytochrome b5 reductase 3 P00387 Details Calcineurin subunit B type 1 P63098 Details Golgi-associated plant pathogenesis-related protein 1 Q9H4G4 Details ADP-ribosylation factor 4 P18085 Details cAMP-dependent protein kinase catalytic subunit alpha P17612 Details Glycylpeptide N-tetradecanoyltransferase 2 O60551 Details ADP-ribosylation factor 1 P84077 Details 60S ribosomal protein L15 P61313 Details ADP-ribosylation factor 6 P62330 Details Tyrosine-protein kinase Lyn P07948 Details Glycylpeptide N-tetradecanoyltransferase 1 P30419 Details cAMP-dependent protein kinase catalytic subunit beta P22694 Details Guanine nucleotide-binding protein G(i) subunit alpha-1 P63096 Details ADP-ribosylation factor-like protein 1 P40616 Details Neuronal calcium sensor 1 P62166 Details Calcineurin B homologous protein 1 Q99653 Details 40S ribosomal protein S8 P62241 Details