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.

PubMed ID
25255805 [ View in PubMed
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Abstract

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
NameUniProt ID
NADH-cytochrome b5 reductase 3P00387Details
Calcineurin subunit B type 1P63098Details
Golgi-associated plant pathogenesis-related protein 1Q9H4G4Details
ADP-ribosylation factor 4P18085Details
cAMP-dependent protein kinase catalytic subunit alphaP17612Details
Glycylpeptide N-tetradecanoyltransferase 2O60551Details
ADP-ribosylation factor 1P84077Details
60S ribosomal protein L15P61313Details
ADP-ribosylation factor 6P62330Details
Tyrosine-protein kinase LynP07948Details
Glycylpeptide N-tetradecanoyltransferase 1P30419Details
cAMP-dependent protein kinase catalytic subunit betaP22694Details
Guanine nucleotide-binding protein G(i) subunit alpha-1P63096Details
ADP-ribosylation factor-like protein 1P40616Details
Neuronal calcium sensor 1P62166Details
Calcineurin B homologous protein 1Q99653Details
40S ribosomal protein S8P62241Details