Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
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DOI：
10.1038/ncomms5919
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发表时间：
2014-09-26
影响因子：
16.6
通讯作者：
Tate, Edward W.
中科院分区：
文献类型：
--
作者：
Thinon, Emmanuelle;Serwa, Remigiusz A.;Broncel, Malgorzata;Brannigan, James A.;Brassat, Ute;Wright, Megan H.;Heal, William P.;Wilkinson, Anthony J.;Mann, David J.;Tate, Edward W.
蛋白质N-豆蔻酰化是一种普遍存在的共翻译和翻译后修饰，其与一系列人类疾病的发生和进展有关。在这里，我们报告的全球N-豆蔻酰化蛋白质组在人类细胞中确定使用定量化学蛋白质组学结合有效的和特定的人类N-豆蔻酰转移酶（NMT）抑制。在正常生长或细胞凋亡期间N-豆蔻酰化的整体定量允许鉴定>100种N-豆蔻酰化蛋白，其中>95%首次在内源性水平上鉴定。此外，在蛋白质组中同时测定了>70种底物的N-豆蔻酰化抑制的定量剂量反应。小分子抑制通过一个保守的底物结合口袋也证明了解决的晶体结构的结合NMT 1和NMT 2。所呈现的数据除了验证用于活细胞中NMT的药理学抑制的工具之外，还大大扩展了共翻译和翻译后N-豆蔻酰化的已知库。 蛋白质N-豆蔻酰化是一种普遍存在的修饰，涉及多种细胞过程的调节。在此，Thinon等人报道了鉴定人细胞中N-肉豆蔻酰化蛋白质并鉴定N-肉豆蔻酰转移酶的100多种内源性翻译后和共翻译底物的通用方法的开发。
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. Protein N-myristoylation is a ubiquitous modification implicated in the regulation of multiple cellular processes. Here, Thinon et al. report the development of a general method to identify N-myristoylated proteins in human cells and identify over 100 endogenous post- and co-translational substrates of N-myristoyltransferase.
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影响因子：
18.3
作者：
Hang, Howard C.;Wilson, John P.;Charron, Guillaume
通讯作者：
Charron, Guillaume
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
30.8
作者：
Cordeddu, Viviana;Di Schiavi, Elia;Pennacchio, Len A.;Ma'ayan, Avi;Sarkozy, Anna;Fodale, Valentina;Cecchetti, Serena;Cardinale, Alessio;Martin, Joel;Schackwitz, Wendy;Lipzen, Anna;Zampino, Giuseppe;Mazzanti, Laura;Digilio, Maria C.;Martinelli, Simone;Flex, Elisabetta;Lepri, Francesca;Bartholdi, Deborah;Kutsche, Kerstin;Ferrero, Giovanni B.;Anichini, Cecilia;Selicorni, Angelo;Rossi, Cesare;Tenconi, Romano;Zenker, Martin;Merlo, Daniela;Dallapiccola, Bruno;Iyengar, Ravi;Bazzicalupo, Paolo;Gelb, Bruce D.;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.9
作者：
Heal, William P.;Jovanovic, Biljana;Tate, Edward W.
通讯作者：
Tate, Edward W.