An Emerging Way for Bacteria to Engage with Host Cells via Protein ADP-riboxanation DOI Creative Commons
Wei Xian, Zhiheng Tang, Qinxin Zhang

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(11), P. 467 - 467

Published: Nov. 1, 2024

Post-translational modifications (PTMs) are increasingly recognized as important strategies used by bacterial pathogens to modulate host cellular functions. Protein ADP-riboxanation, a derivative of ADP-ribosylation, has recently emerged new biochemical way which interact with cells. Recent studies have revealed that this modification broad regulatory roles in processes including cell death, protein translation, and stress granule formation. Given the vast majority ADP-riboxanases still uncharacterized, review we also highlight utility advanced proteomic tools functional dissection ADP-riboxanation events during infections.

Language: Английский

Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose DOI Creative Commons
Daniel S. Bejan,

Rachel E. Lacoursiere,

Jonathan N. Pruneda

et al.

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract The prevailing view on post-translational modifications (PTMs) is that a single amino acid modified with PTM at any given time. However, recent work has demonstrated crosstalk between different PTMs, some occurring the same residue. Such interplay seen ADP-ribosylation and ubiquitylation. For example, DELTEX E3 ligases were reported to ubiquitylate hydroxyl group free NAD + ADP-ribose in vitro, generating noncanonical ubiquitin ester-linked species. In this report, we show, for first time, dual occurs cells mono-ADP-ribosylated (MARylated) PARP10 Glu/Asp sites form MAR ester. We call process mono-ADP-ribosyl ubiquitylation or MARUbylation. Using chemical enzymatic treatments, including newly characterized bacterial deubiquitinase esterase-specific activity, discovered multiple PARPs are MARUbylated extended K11-linked polyubiquitin chains when exogenously expressed. Finally, show response type I interferon stimulation, MARUbylation can occur endogenously PARP targets. Thus, represents new broadens our understanding of function PARP-mediated cells.

Language: Английский

Citations

3
A family of bacterial Josephin-like deubiquitinases with an irreversible cleavage mode DOI Creative Commons
Thomas Hermanns, Susanne Kolek, Matthias Uthoff

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

2
Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy DOI Creative Commons
Daniela Spano, Giuliana Catara

Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 29 - 29

Published: Dec. 22, 2023

Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects various signaling pathways. can alter molecular functions tagged substrates respect protein turnover, biological activity, subcellular localization or protein–protein interaction. As result, wide variety cellular processes are under ubiquitination-mediated control, contributing maintenance homeostasis. It follows that dysregulation ubiquitination reactions plays relevant role in pathogenic states human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, enzymes ubiquitin–proteasome system (UPS), including E3 ligases deubiquitinases (DUBs), have attracted attention novel druggable targets for development new anticancer therapeutic approaches. This perspective article summarizes peculiarities shared by involved reaction which, when deregulated, lead tumorigenesis. Accordingly, an overview main pharmacological interventions targeting UPS clinical use still trials provided, also highlighting limitations efficacy these Therefore, attempts circumvent drug resistance side well UPS-related emerging technologies therapeutics discussed.

Language: Английский

Citations

29
The emerging roles of non-canonical ubiquitination in proteostasis and beyond DOI Creative Commons

Yoshino Akizuki,

Stephanie Kaypee, Fumiaki Ohtake

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)

Published: March 22, 2024

Ubiquitin regulates various cellular functions by posttranslationally modifying substrates with diverse ubiquitin codes. Recent discoveries of new chain topologies, types bonds, and non-protein have substantially expanded the complexity code. Here, we describe system covering basic principles recent related to mechanisms, technologies, biological importance.

Language: Английский

Citations

10
Mechanisms and Therapeutic Strategies for NLRP3 Degradation via Post-Translational Modifications in Ubiquitin-proteasome and Autophagy Lysosomal Pathway DOI

Kaiyue Su,

Minghai Tang, Jie Wu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117476 - 117476

Published: March 4, 2025

Language: Английский

Citations

1
Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system DOI
Cameron G. Roberts, Tyler G. Franklin, Jonathan N. Pruneda

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(18)

Published: Aug. 9, 2023

Language: Английский

Citations

19
Specificities and redundancies in the NEL family of bacterial E3 ubiquitin ligases of Salmonella enterica serovar Typhimurium DOI Creative Commons
Andrea Bullones-Bolaños,

Paula Martín-Muñoz,

Claudia Vallejo-Grijalba

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Salmonella enterica serovar Typhimurium expresses two type III secretion systems, T3SS1 and T3SS2, which are encoded in pathogenicity island 1 (SPI1) SPI2, respectively. These essential virulent factors that secrete more than 40 effectors translocated into host animal cells. This study focuses on three of these effectors, SlrP, SspH1, SspH2, members the NEL family E3 ubiquitin ligases. We compared their expression, regulation, translocation patterns, role cell invasion intracellular proliferation, ability to interact ubiquitinate specific partners, effect cytokine secretion. found transcription genes encoding depends virulence regulator PhoP. Although have potential be secreted through SspH1 SspH2 is largely restricted T3SS2 due expression pattern. detected a for proliferation inside fibroblasts masked by redundancy. The generation chimeric proteins allowed us demonstrate N-terminal part proteins, containing leucine-rich repeat motifs, confers specificity towards ubiquitination targets. Furthermore, polyubiquitination patterns generated were different each effector, with Lys48 linkages being predominant SspH2. Finally, our experiments support an anti-inflammatory

Language: Английский

Citations

5
In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases DOI Creative Commons
Marta Campos Alonso, Klaus‐Peter Knobeloch

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 22, 2024

Proteases that cleave ubiquitin or ubiquitin-like proteins (UBLs) are critical players in maintaining the homeostasis of organism. Concordantly, their dysregulation has been directly linked to various diseases, including cancer, neurodegeneration, developmental aberrations, cardiac disorders and inflammation. Given potential as novel therapeutic targets, it is essential fully understand mechanisms action. Traditionally, observed effects resulting from deficiencies deubiquitinases (DUBs) UBL proteases have often attributed misregulation substrate modification by UBLs. Therefore, much research focused on understanding catalytic activities these proteins. However, this view overlooked possibility DUBs might also significant non-catalytic functions, which more prevalent than previously believed urgently require further investigation. Moreover, multiple examples shown either selective loss only protease activity complete absence can different functional physiological consequences. Furthermore, contain domains binding motifs not modulate but mediate entirely functions. This review aims shed light non-catalytic, moonlighting functions proteases, extend beyond hydrolysis chains just beginning emerge.

Language: Английский

Citations

5
Genetic Code Expansion Approaches to Decipher the Ubiquitin Code DOI Creative Commons

Vera Wanka,

Maximilian Fottner, Marko Cigler

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(20), P. 11544 - 11584

Published: Sept. 23, 2024

The covalent attachment of Ub (ubiquitin) to target proteins (ubiquitylation) represents one the most versatile PTMs (post-translational modifications) in eukaryotic cells. Substrate modifications range from a single moiety being attached protein complex chains that can also contain Ubls (Ub-like proteins). Ubiquitylation plays pivotal roles aspects biology, and cells dedicate an orchestrated arsenal enzymes install, translate, reverse these modifications. entirety this system is coined code. Deciphering code challenging due difficulty reconstituting enzymatic machineries generating defined Ub/Ubl-protein conjugates. This Review provides comprehensive overview recent advances using GCE (genetic expansion) techniques study We highlight strategies site-specifically ubiquitylate discuss their advantages disadvantages, as well various applications. Additionally, we review potential small chemical targeting Ub/Ubls present GCE-based approaches additional layer complexity. Furthermore, explore methods rely on develop tools probe interactors offer insights into how future could help unravel complexity

Language: Английский

Citations

4
A new hybrid post-translational modification—have you lost your (MARUb)les? DOI Creative Commons
Isaac de Araújo Matos, Nícolas C. Hoch

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Recent work in The EMBO Journal describes a new hybrid post-translational modification of proteins, composed poly-ubiquitin chain that is attached to target protein via mono-ADP-ribose (MAR) moiety. This "MARUbylation" likely play important functions during interferon signalling, core component innate immunity.

Language: Английский

Citations

0