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@article{Thinon:2016:10.1021/acschembio.6b00371,
author = {Thinon, E and Morales, Sanfrutos J and Mann, D and Tate, EW},
doi = {10.1021/acschembio.6b00371},
journal = {ACS Chemical Biology},
pages = {2165--2176},
title = {N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells},
url = {http://dx.doi.org/10.1021/acschembio.6b00371},
volume = {11},
year = {2016}
}
TY - JOUR
AB - N-Myristoyltransferase (NMT) covalently attaches a C14-fatty acid to the N-terminal glycine of proteins and has been proposed as a therapeutic target in cancer. We have recently shown that selective NMT inhibition leads to dose-responsive loss of N-myristoylation on more than 100 protein targets in cells, and cytotoxicity in cancer cells. N-myristoylation lies upstream of multiple pro-proliferative and oncogenic pathways, but to date the complex substrate specificity of NMT has limited determination of which diseases are most likely to respond to a selective NMT inhibitor. We describe here the phenotype of NMT inhibition in HeLa cells, and show that cells die through apoptosis following or concurrent with accumulation in G1 phase. We used quantitative proteomics to map protein expression changes for more than 2700 proteins in response to treatment with an NMT inhibitor in HeLa cells, and observed down-regulation of proteins involved in cell cycle regulation, and up-regulation of proteins involved in the endoplasmic reticulum stress and unfolded protein response, with similar results in breast (MCF-7, MDA-MB-231) and colon (HCT116) cancer cell lines. This study describes the cellular response to NMT inhibition at the proteome level, and provides a starting point for selective targeting of specific diseases with NMT inhibitors, potentially in combination with other targeted agents.
AU - Thinon,E
AU - Morales,Sanfrutos J
AU - Mann,D
AU - Tate,EW
DO - 10.1021/acschembio.6b00371
EP - 2176
PY - 2016///
SN - 1554-8937
SP - 2165
TI - N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells
T2 - ACS Chemical Biology
UR - http://dx.doi.org/10.1021/acschembio.6b00371
UR - http://hdl.handle.net/10044/1/33254
VL - 11
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821