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

Thinon, Emmanuelle; Serwa, Remigiusz A.; Broncel, Malgorzata; Brannigan, J.A.; Brassat, Ute; Wright, Megan H.; Heal, William P.; Wilkinson, Anthony J.; Mann, David J.; Tate, Edward W.

doi:10.1038/ncomms5919

Cited by 207 publications

(343 citation statements)

References 67 publications

(79 reference statements)

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“…FRS2α contains the MGXXXS/T consensus sequence at the N-terminus for N-myristoylation modification (10). N-myristoyltransferase (NMT) catalyzes the myristoylation modification process by transferring the myristoyl group from myristoylCoA to the glycine at the N-terminus of a protein (15). In this study, we investigated a therapeutic approach to inhibit FGF/FGFRs-mediated oncogenic signaling and proliferation of cancer cells by blocking myristoylation of FRS2α.…”

Section: Inhibiting Myristoylation Of Frs2α In Fgfr-mediated Tumorsmentioning

confidence: 99%

Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression

Li¹,

Alsaidan²,

Ma³

et al. 2018

Journal of Biological Chemistry

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Section: Inhibiting Myristoylation Of Frs2α In Fgfr-mediated Tumorsmentioning

confidence: 99%

Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression

Li¹,

Alsaidan²,

Ma³

et al. 2018

Journal of Biological Chemistry

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“…Computational prediction suggested that about 0.5% of all proteins in the human genome could be myristoylated (Maurer-Stroh et al, 2004). Indeed, the N-myristoylated proteome was recently studied in human cells, leading to the identification of more than 100 N-myristoylated proteins (Thinon et al, 2014). The myristoylated proteins include key components in intracellular signaling pathways, oncogenes, structural viral proteins but also common constitutive eukaryotic proteins.…”

Section: Myristic Acid and Protein N-terminal Myristoylationmentioning

confidence: 99%

Fatty acid acylation of proteins: specific roles for palmitic, myristic and caprylic acids

Rioux¹

2016

OCL

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-Fatty acid acylation of proteins corresponds to the co-or post-translational covalent linkage of an acyl-CoA, derived from a fatty acid, to an amino-acid residue of the substrate protein. The cellular fatty acids which are involved in protein acylation are mainly saturated fatty acids. Palmitoylation (S-acylation) corresponds to the reversible attachment of palmitic acid (C16:0) via a thioester bond to the side chain of a cysteine residue. N-terminal myristoylation refers to the covalent attachment of myristic acid (C14:0) by an amide bond to the N-terminal glycine of many eukaryotic and viral proteins. Octanoylation (O-acylation) typically concerns the formation of an ester bond between octanoic acid (caprylic acid, C8:0) and the side chain of a serine residue of the stomach peptide ghrelin. An increasing number of proteins (enzymes, hormones, receptors, oncogenes, tumor suppressors, proteins involved in signal transduction, eukaryotic and viral structural proteins) have been shown to undergo fatty acid acylation. The addition of the acyl moiety is required for the protein function and usually mediates protein subcellular localization, protein-protein interaction or protein-membrane interaction. Therefore, through the covalent modification of proteins, these saturated fatty acids exhibit emerging specific and important roles in modulating protein functions. This review provides an overview of the recent findings on the various classes of protein acylation leading to the biological ability of saturated fatty acids to regulate many pathways. Finally, the nutritional links between these elucidated biochemical mechanisms and the physiological roles of dietary saturated fatty acids are discussed. L'acylation concerne de très nombreuses protéines (enzymes, hormones, récepteurs, oncogènes, suppresseurs de tumeur, protéines impliquées dans la transduction des signaux, protéines de structure eucaryotes et même virales) et exerce donc une grande variété de fonctions dans les régulations cellulaires. La liaison covalente de l'acide gras à la protéine est cruciale pour l'acquisition de la fonction de la protéine, en changeant son hydrophobicité, en régulant l'ancrage de la protéine à la membrane, en modifiant son adressage subcellulaire ou encore en induisant des interactions entre sous-unités protéiques. La découverte progressive de nombreuses protéines acylées, dont la fonction est régulée par l'acylation, donne donc un nouvel intérêt fonctionnel à ces acides gras saturés. L'objectif de cette revue est de synthétiser les découvertes récentes sur les différentes classes d'acylation des protéines et sur les fonctions cellulaires émergentes que cette acylation procure à certains acides gras saturés. Le lien nutritionnel entre ces mécanismes moléculaires et les apports alimentaires en acides gras saturés est finalement discuté.

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“…Functionalized lipidation probes have been used to prove the exploitation of host-cell-mediated prenylation for membrane targeting of Legionella effectors (Ivanov et al 2010). Probes for a number of additional lipid modifications have been published and used to study a variety of diseases such as malaria and cancer (Thinon et al 2014;Wright et al 2014;Tate et al 2015). These could be useful to determine if T4SS effectors exploit other lipid modifications as membrane anchors.…”

Section: Functionalized Substrate Analogues To Profile Ptmsmentioning

confidence: 99%

Creating a customized intracellular niche: subversion of host cell signaling byLegionellatype IV secretion system effectors

Mattheis

Tate

et al. 2015

Can. J. Microbiol.

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Abstract:The Gram-negative facultative intracellular pathogen Legionella pneumophila infects a wide range of different protozoa in the environment and also human alveolar macrophages upon inhalation of contaminated aerosols. Inside its hosts, it creates a defined and unique compartment, termed the Legionella-containing vacuole (LCV), for survival and replication. To establish the LCV, L. pneumophila uses its Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effector proteins into the host cell. Although it has become apparent in the past years that these effectors subvert a multitude of cellular processes and allow Legionella to take control of host cell vesicle trafficking, transcription, and translation, the exact function of the vast majority of effectors still remains unknown. This is partly due to high functional redundancy among the effectors, which renders conventional genetic approaches to elucidate their role ineffective. Here, we review the current knowledge about Legionella T4SS effectors, highlight open questions, and discuss new methods that promise to facilitate the characterization of T4SS effector functions in the future.Key words: Legionella, type IV secretion system, effectors, Legionella-containing vacuole.Résumé : Le pathogène intracellulaire facultatif à Gram négatif Legionella pneumophila infecte une large gamme de différents protozoaires environnementaux de même que les macrophages alvéolaires humains des suites de l'inhalation d'aérosols contaminés. À l'intérieur de ses hôtes, il crée un compartiment précis et unique nommé vacuole contenant Legionella (« Legionella-containing vacuole », LCV) pour sa survie et sa multiplication. Afin d'établir une LCV, L. pneumophila utilise sont système de sécrétion de type IV (SST4) Dot/Icm, rendant possible la translocation de plus de 300 protéines effectrices dans la cellule hôte. Au cours des dernières années, on a établi que ces effecteurs subvertissent une multitude de processus cellulaires et permettent à Legionella de prendre le contrôle du trafic cellulaire, de la transcription et de la traduction. Or, la fonction exacte de la grande majorité des effecteurs est toujours inconnue. L'importante redondance fonctionnelle au sein des effecteurs explique en partie cette incertitude et invalide les approches génétiques conventionnelles adoptées pour élucider leur rôle. Dans le présent ouvrage, nous passons en revue les connaissances actuelles entourant les effecteurs SST4 de Legionella, faisons ressortir certaines interrogations, et abordons de nouvelles méthodes qui promettent de faciliter la caractérisation de la fonction des effecteurs SST4. [Traduit par la Rédaction] Mots-clés : Legionella, système de sécrétion de type IV, effecteurs, vacuole contenant Legionella.

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

Cited by 207 publications

References 67 publications

Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression

Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression

Fatty acid acylation of proteins: specific roles for palmitic, myristic and caprylic acids

Creating a customized intracellular niche: subversion of host cell signaling byLegionellatype IV secretion system effectors

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