Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation

Zhang, Li; Ding, Xiaojun; Cui, Jixin; Xu, Hao; Chen, Jing; Gong, Yi-Nan; Hu, Liyan; Zhou, Yan; Ge, Jianning; Lu, Qiuhe; Liu, Liping; Chen, She; Shao, Feng

doi:10.1038/nature10690

Cited by 170 publications

(162 citation statements)

References 35 publications

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“…The NleE protein of pathogenic E. coli is a methyltransferase with a unique structural fold that can modify the human TAB2 and TAB3 proteins involved in NF-κB signaling to blunt the inflammatory response against the bacterium (96)(97)(98). Interestingly, the modified cysteine residue in these proteins is also coordinated to a zinc ion, although the significance of this ligation is unclear.…”

Section: Cysteine S-methylationmentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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Cellular physiology depends on the alteration of protein structures by covalent modification reactions. Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for posttranslationally methylated amino acid residues and for the enzymes that catalyze these modifications. These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation. Two of these enzymes may modify their substrates during ribosomal assembly because the final methylated histidine and arginine residues are buried deep within the ribosome with contacts only with RNA. Two of these modifications occur broadly in eukaryotes, including humans, while the others demonstrate a more limited phylogenetic range. Analysis of strains where the methyltransferase genes are deleted has given insight into the physiological roles of these modifications. These reactions described here add diversity to the modifications that generate the typical methylated lysine and arginine residues previously described in histones and other proteins. Regulation of biological function by protein methylation reactionsIt is more and more apparent just how much of biological function is dependent upon posttranslational modifications (1). The human genome encodes some 900 enzymes catalyzing just protein phosphorylation or ubiquitination (2,3). However, it is now clear that methyl groups can stand beside phosphate groups and ubiquitin as major players in controlling the physiological functions of proteins. We are beginning to understand how the much greater diversity of protein methylation reactions can give rise to a greater diversity of function (1,4-8). We are also learning the importance of crosstalk between protein and DNA methylation reactions (9) and among protein methylation, phosphorylation, acetylation, and ubiquitination reactions (10-12). Finally, we are discovering how alterations in protein methylation pathways can lead to human pathology, particularly in cancer (13-15).The collection of over sixty human protein arginine and lysine methyltransferases that leave histone "marks" recognized by reader proteins to guide gene expression are perhaps the poster children for the importance of protein methyltransferases (16-17). However, recent work has emphasized the importance of methylating non-histone substrates at these residues, particularly ribosomal proteins, translation factors, and transcription factors in a wide variety of organisms (7,8,15,18,19). Furthermore, the methylation of lysine and arginine residues represents just the tip of the iceberg in protein methylation -modifications have also been established at histidine, modified histidine (diphthamide), glutamate, glutamine, asparagine, Lisoaspartate, D-aspartate, cysteine, isoprenylcysteine, me...

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Section: Cysteine S-methylationmentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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“…NleE directly methylates the cysteine residue in the ZnF of TAB2/3 to hinder their ubiquitination, whereas Tir facilitates the binding of host protein tyrosine phosphatases SHP-1 and SHP-2 to TRAF6, which prevents the ubiquitination of TRAF6. 136,137 Finally, EPEC and EHEC also target host neddylation via the Cif effector to favor their survival. Similarly, Burkholderia pseudomallei encodes a Cif homolog effector named CHBP.…”

Section: Shigella Flexnerimentioning

confidence: 99%

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

Chai

Liu

2016

Cell Mol Immunol

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The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host-pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autophagy and apoptosis, all of which are fine-tuned by the ubiquitin system to eradicate the invading pathogens and to reduce concomitant host damage. By contrast, pathogens have evolved a cohort of exquisite strategies to evade host innate immunity by usurping the ubiquitin system for their own benefits. Here, we present recent advances regarding the ubiquitin system-mediated modulation of host-pathogen interplay, with a specific focus on host innate immune defenses and bacterial pathogen immune evasion.

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“…2c). As shown by a recent study, methylation of a Cys residue in NZF domain of either TAB2 or TAB3 disrupts polyubiquitin recognition and blocks NF-jB signaling pathway [49]. Another example is HOIL-1L protein, which is a component of the linear ubiquitin chain assembly complex (LUBAC) [9].…”

Section: Multiple Ubiquitin-binding By a Single Ubdmentioning

confidence: 99%

Selectivity of the ubiquitin‐binding modules

Rahighi

Đikić

2012

FEBS Letters

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a b s t r a c tUbiquitin-binding modules are constituents of cellular proteins that mediate the effects of ubiquitylation by making transient, non-covalent interactions with ubiquitin molecules. While some ubiquitin-binding modules bind single ubiquitin moieties, others are selective for specific ubiquitin chains of different linkage types and lengths. In recent years, functions of ubiquitin chains that are polymerized through their Lys or N-terminal Met (i.e. linear chains) residues have been linked to a variety of cellular processes. Selectivity of ubiquitin-binding modules for different ubiquitin chain types appears as a key to the distinct regulatory consequences during protein quality control pathways, receptor endocytosis, gene transcription, signaling via the NF-jB pathway, and autophagy.

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Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation

Cited by 170 publications

References 35 publications

The ribosome: A hot spot for the identification of new types of protein methyltransferases

The ribosome: A hot spot for the identification of new types of protein methyltransferases

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

Selectivity of the ubiquitin‐binding modules

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