Post-translational modifications in signal integration

Deribe, Yonathan Lissanu; Pawson, Tony; Đikić, Ivan

doi:10.1038/nsmb.1842

Cited by 687 publications

(559 citation statements)

References 97 publications

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“…Indeed, IDPs are more susceptible to undergoing PTMs than folded proteins 1. Because of the inherent flexibility of these proteins, PTMs will have an important impact on their activity, cellular localization, and interaction properties, by modulating their structural dynamics 2, 3, 4, 5, 6, 7, 8. For example, N‐terminal acetylation of α‐synuclein9 increases the helical propensity of the N‐terminal segment7 and enhances the affinity of α‐synuclein for calmodulin by a factor of 10 10.…”

Section: Introductionmentioning

confidence: 99%

N‐Lauroylation during the Expression of Recombinant N‐Myristoylated Proteins: Implications and Solutions

et al. 2015

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Incorporation of myristic acid onto the N terminus of a protein is a crucial modification that promotes membrane binding and correct localization of important components of signaling pathways. Recombinant expression of N‐myristoylated proteins in Escherichia coli can be achieved by co‐expressing yeast N‐myristoyltransferase and supplementing the growth medium with myristic acid. However, undesired incorporation of the 12‐carbon fatty acid lauric acid can also occur (leading to heterogeneous samples), especially when the available carbon sources are scarce, as it is the case in minimal medium for the expression of isotopically enriched samples. By applying this method to the brain acid soluble protein 1 and the 1–185 N‐terminal region of c‐Src, we show the significant, and protein‐specific, differences in the membrane binding properties of lauroylated and myristoylated forms. We also present a robust strategy for obtaining lauryl‐free samples of myristoylated proteins in both rich and minimal media.

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Section: Introductionmentioning

confidence: 99%

N‐Lauroylation during the Expression of Recombinant N‐Myristoylated Proteins: Implications and Solutions

et al. 2015

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“…They can be reversible (e.g., acetylation) or irreversible (e.g., proteolytic cleavage), enzyme catalysed (e.g., kinase-mediated phosphorylation) or the result direct chemical reaction (e.g., oxidation), and individual or combinatorial [6,7]. In toto , these factors comprise a well-adapted basis for signalling, regulation, targeting, and interaction, all at least potentially in the absence of de novo protein synthesis [3,8]. …”

Section: Introductionmentioning

confidence: 99%

“…This is in part because reversible phosphorylation is a component of both cellular signalling [8,12] and direct regulatory control of protein function [13-15]. Protein phosphorylation can be stoichiometric at an individual site, or combinatorial and sequential/hierarchical at multiple sites [16,17].…”

Section: Introductionmentioning

confidence: 99%

Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation

Rao

Thelen

et al. 2013

BMC Bioinformatics

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BackgroundReversible posttranslational protein modifications such as phosphorylation of Ser/Thr/Tyr and Met oxidation are critical for both metabolic regulation and cellular signalling. Although these modifications are typically studied individually, herein we describe the potential for cross-talk and hierarchical regulation.ResultsThe proximity of Met to Ser/Thr/Tyr within the proteome has not previously been addressed. In order to consider the possibility of a generalized interaction, we performed a trans-kingdom sequence analysis of known phosphorylation sites in proteins from bacteria, fungi, plants, and animals. The proportion of phosphorylation sites that include a Met within a 13-residue window centered upon Ser/Thr/Tyr is significantly less than the occurrence of Met in proximity to all Ser/Thr/Tyr residues. Met residues are present at all positions (-6 to +6, inclusive) within the 13-residue window that we have considered. Detailed analysis of sequences from eight disparate plant taxa revealed that many conserved phosphorylation sites have a Met residue in the proximity. Results from GO enrichment analysis indicated that the potential for phosphorylation and Met oxidation crosstalk is most prevalent in kinases and proteins involved in signalling.ConclusionThe large proportion of known phosphorylation sites with Met in the proximity fulfils the necessary condition for cross-talk. Kinases/signalling proteins are enriched for Met around phosphorylation sites. These proteins/sites are likely candidates for cross-talk between oxidative signalling and reversible phosphorylation.

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“…This very diverse set of modifications include phosphorylations, acetylations, sumoylations, ubiquitinations, ADP-ribosylations, nitrations and many others [1]. PTMs are highly dynamic processes and most of them result from the activity of antagonizing enzymes (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…kinases vs. phosphatases, acetylases vs. deacetylases, etc). Numerous studies have highlighted the important role of PTMs in signaling pathways, allowing a crosstalk between the cell and its environment and endowing the cell with a certain flexibility towards change [1]. In this context, nicotinamide adenine dinucleotide (NAD) has gained a renewed interest as an important substrate for a series of enzymes catalyzing a set of post-translational modifications, such as deacetylation or ADP-ribosylation.…”

Section: Introductionmentioning

confidence: 99%

Sirtuins and inflammation: Friends or foes?

Gallí

Gool

Léo

2011

Biochemical Pharmacology

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Lysine acetylation/deacetylation has been recognized as an important posttranslational modification regulating numerous cellular processes. Sirtuins represent novel players in these complex regulatory circuits. These NAD-dependent lysine-deacetylases have attracted much interest based on their role in the regulation of lifespan in lower organisms, and their capacity to interfere with cell growth, proliferation and survival in response to stress. Their absolute requirement for NAD suggests that these enzymes may represent an important molecular link between metabolism and several human disorders such as diabetes and cancer. More recently, the identification of several transcription factors known to play a role in the immune system as sirtuin substrates has suggested that this family of enzymes may also play an important role in the regulation of inflammation, a pathological situation with clear links to metabolism and ageing in humans. We review herein the possible links between nuclear sirtuins and the regulation of an immune response, and discuss the possible strategies that may lead to the development of novel therapeutic approaches to treat inflammation by targeting sirtuin activity.

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Post-translational modifications in signal integration

Cited by 687 publications

References 97 publications

N‐Lauroylation during the Expression of Recombinant N‐Myristoylated Proteins: Implications and Solutions

N‐Lauroylation during the Expression of Recombinant N‐Myristoylated Proteins: Implications and Solutions

Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation

Sirtuins and inflammation: Friends or foes?

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