Post-translational regulation of ubiquitin signaling

The Journal of Cell Biology, Journal Year: 2019, Volume and Issue: 218(6), P. 1776 - 1786

Published: April 18, 2019

Ubiquitination regulates many essential cellular processes in eukaryotes. This post-translational modification (PTM) is typically achieved by E1, E2, and E3 enzymes that sequentially catalyze activation, conjugation, ligation reactions, respectively, leading to covalent attachment of ubiquitin, usually lysine residues substrate proteins. Ubiquitin can also be successively linked one the seven on ubiquitin form distinctive forms polyubiquitin chains, which, depending upon used length dictate fate Recent discoveries revealed this code further expanded PTMs such as phosphorylation, acetylation, deamidation, ADP-ribosylation, components ubiquitination machinery, or both. These provide additional regulatory nodes integrate development insulting signals with homeostasis. Understanding precise roles these regulation signaling will new insights into mechanisms treatment various human diseases ubiquitination, including neurodegenerative diseases, cancer, infection, immune disorders.

Language: Английский

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An expanded lexicon for the ubiquitin code

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 273 - 287

Published: Oct. 25, 2022

Language: Английский

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The ubiquitin codes in cellular stress responses

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(3), P. 157 - 190

Published: July 19, 2023

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components numerous biological processes undergo ubiquitination mammalian cells upon exposure to diverse stresses, from exogenous factors reactions, causing a dazzling variety functional consequences. Various forms ubiquitin signals generated by ubiquitylation events specific milieus, known as codes, constitute an intrinsic part myriad stress responses. These events, leading proteolytic turnover substrates or just switch functionality, initiate, regulate, supervise multiple stress-associated responses, supporting adaptation, homeostasis recovery, and survival stressed cells. In this review, we attempted summarize crucial roles response different environmental intracellular while discussing how stresses modulate system. This review also updates recent advances understanding machinery well responses discusses some important questions may warrant future investigation.

Language: Английский

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Ubiquitin—A structural perspective

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 323 - 346

Published: Jan. 1, 2025

Language: Английский

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Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases

Science, Journal Year: 2019, Volume and Issue: 364(6442), P. 787 - 792

Published: May 23, 2019

Divergent protein kinase SidJ is a produced by Legionella pneumophila that orchestrates this intracellular pathogen's establishment within the host cell. prevents lysosome fusion with vacuole, which bacterium resides and replicates. also modulates toxicity of SidE family ubiquitin ligases catalyze phosphoribosyl-linked ubiquitination. Black et al. discovered activated calmodulin. Furthermore, although has pseudokinase fold, it does not phosphorylate proteins but polyglutamylates them instead. The in vivo relevance mechanism for bacterial infectivity was verified natural reservoir Acanthamoeba castellanii . Science , issue p. 787

Language: Английский

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Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(1), P. 164 - 179.e6

Published: Nov. 12, 2019

The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity Legionella pneumophila. Here, we describe identification two effectors that reverse PR are thus named deubiquitinases for (DUPs; DupA DupB). Structural analyses revealed ubiquitin ligases harbor a highly homologous catalytic phosphodiesterase (PDE) domain. However, unlike ligases, displays increased affinity to PR-ubiquitinated substrates, which allows cleave from substrates. Interfering with DupA-ubiquitin binding switches its activity toward SidE-type ligase. Given the high exploited catalytically inactive mutant trap identify more than 180 host proteins in Legionella-infected cells. Proteins involved endoplasmic reticulum (ER) fragmentation membrane recruitment Legionella-containing vacuoles (LCV) emerged as major targets. global map substrates provides critical insights into host-pathogen interactions during infection.

Language: Английский

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Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination

Nature, Journal Year: 2018, Volume and Issue: 557(7707), P. 734 - 738

Published: May 1, 2018

Language: Английский

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Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain–containingLegionellaeffectors

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(47), P. 23518 - 23526

Published: Nov. 5, 2019

Posttranslational protein modification by ubiquitin (Ub) is a central eukaryotic mechanism that regulates plethora of physiological processes. Recent studies unveiled an unconventional type ubiquitination mediated the SidE family Legionella pneumophila effectors, such as SdeA, catalyzes conjugation Ub to serine residue target proteins via phosphoribosyl linker (hence named PR-ubiquitination). Comparable deubiquitinases in canonical pathway, here we show 2 paralogous Lpg2154 (DupA; deubiquitinase for PR-ubiquitination) and Lpg2509 (DupB), reverse PR-ubiquitination specific removal phosphoribosyl-Ub from substrates. Both DupA DupB are fully capable rescuing Golgi fragmentation phenotype caused exogenous expression SdeA mammalian cells. We further deletion these genes results significant accumulation PR-ubiquitinated species host cells infected with In addition, have identified list targets play role modulating association Legionella-containing vacuoles. Together, our data establish complete deubiquitination cycle demonstrate intricate control has over this unusual Ub-dependent posttranslational modification.

Language: Английский

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A new dawn beyond lysine ubiquitination

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(8), P. 802 - 811

Published: July 27, 2022

Language: Английский

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Non-lysine ubiquitylation: Doing things differently

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 19, 2022

The post-translational modification of proteins with ubiquitin plays a central role in nearly all aspects eukaryotic biology. Historically, studies have focused on the conjugation to lysine residues substrates, but it is now clear that ubiquitylation can also occur cysteine, serine, and threonine residues, as well N-terminal amino group proteins. Paradigm-shifting reports non-proteinaceous substrates further extended reach beyond proteome include intracellular lipids sugars. Additionally, results from bacteria revealed novel ways ubiquitylate (and deubiquitylate) without need for any enzymatic components canonical cascade. Focusing mainly upon recent findings, this review aims outline current understanding non-lysine speculate molecular mechanisms physiological importance non-canonical modification.

Language: Английский

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