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Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Title: Global profiling of co- and post-translationally N-myristoylated proteomes in human cells
Authors: Thinon, E
Serwa, RA
Broncel, M
Brannigan, JA
Brassat, U
Wright, MH
Heal, WP
Wilkinson, AJ
Mann, DJ
Tate, EW
Item Type: Journal Article
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.
Issue Date: 1-Sep-2014
Date of Acceptance: 5-Aug-2014
URI: http://hdl.handle.net/10044/1/18701
DOI: 10.1038/ncomms5919
ISSN: 2041-1723
Publisher: Nature Research
Start Page: 1
End Page: 13
Journal / Book Title: Nature Communications
Volume: 5
Copyright Statement: © 2014 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: BB/D02014X/1
G0900278
n/a
EP/K039946/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
QUANTITATIVE PROTEOMICS
CHEMICAL REPORTERS
PROTEIN-KINASE
DATA QUALITY
MYRISTOYLTRANSFERASE
APOPTOSIS
IDENTIFICATION
PATHWAY
REPLACEMENT
INHIBITORS
Acyltransferases
Crystallography, X-Ray
HeLa Cells
Humans
Myristic Acid
Protein Processing, Post-Translational
Proteome
Hela Cells
Humans
Acyltransferases
Myristic Acid
Proteome
Crystallography, X-Ray
Protein Processing, Post-Translational
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
QUANTITATIVE PROTEOMICS
CHEMICAL REPORTERS
PROTEIN-KINASE
DATA QUALITY
MYRISTOYLTRANSFERASE
APOPTOSIS
IDENTIFICATION
PATHWAY
REPLACEMENT
INHIBITORS
Publication Status: Published
Article Number: ARTN 4919
Online Publication Date: 2014-09-26
Appears in Collections:Chemistry
Biological and Biophysical Chemistry
Faculty of Natural Sciences



This item is licensed under a Creative Commons License Creative Commons