{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:14:18Z","timestamp":1778505258546,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013522","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100137"],"award-info":[{"award-number":["32100137"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370185"],"award-info":[{"award-number":["32370185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200141"],"award-info":[{"award-number":["32200141"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270185"],"award-info":[{"award-number":["32270185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470179"],"award-info":[{"award-number":["32470179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82225028"],"award-info":[{"award-number":["82225028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172287"],"award-info":[{"award-number":["82172287"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2021YFC2301403"],"award-info":[{"award-number":["2021YFC2301403"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Legionella pneumophila<\/jats:italic>, the causative agent of Legionnaires\u2019 disease, exists ubiquitously in natural and artificial water systems. This pathogen poses serious threat to human health. One salient feature of <jats:italic>L. pneumophila<\/jats:italic> pathogenesis is the hundreds of effectors delivered into host cells by its Dot\/Icm transporter. These virulence factors interfere with multiple hosts signaling pathways to subvert host defense. The ubiquitin network is essential in host signaling involved in immunity and thus is a common target of <jats:italic>L. pneumophila<\/jats:italic> effectors. At least thirteen Dot\/Icm effectors have been shown to function as E3 ubiquitin ligases that cooperate with the host ubiquitination machinery by distinct mechanisms. In addition, seven deubiquitinases (DUBs) have been characterized. Furthermore, effectors that utilize catalysis mechanisms that are chemically distinct from the canonical one found in eukaryotes have been reported, indicating that hijacking of the host ubiquitin network by <jats:italic>L. pneumophila<\/jats:italic> is extensive and complex. Here, we identified ubiquitin interacting proteins with a proximity labeling method and found that the effector Lug14 (Lpg1106) functions as a novel ubiquitin ligase. Lug14 works with the E2 UbcH5c to catalyze ubiquitination with a preference for K<jats:sub>11<\/jats:sub>-linked chains by a mechanism that does not require a cysteine residue. Finally, we found that Lug14 targets ARIH2, a member of the host RBR E3 ligase family, leading to increased activation of the NLRP3 inflammasome in macrophages.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013522","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:47:37Z","timestamp":1757958457000},"page":"e1013522","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of host immunity by a novel Legionella pneumophila E3 ubiquitin ligase"],"prefix":"10.1371","volume":"21","author":[{"given":"Shuxin","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao-Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxiuli","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songying","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-6621","authenticated-orcid":true,"given":"Zhao-Qing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ppat.1013522.ref001","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The ubiquitin system","volume":"67","author":"A Hershko","year":"1998","journal-title":"Annu Rev Biochem"},{"issue":"6","key":"ppat.1013522.ref002","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrmicro3259","article-title":"Exploitation of the host ubiquitin system by human bacterial pathogens","volume":"12","author":"H Ashida","year":"2014","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1013522.ref003","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.chom.2007.02.003","article-title":"Bacterial interference of ubiquitination and deubiquitination","volume":"1","author":"A Rytk\u00f6nen","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ppat.1013522.ref004","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fcimb.2017.00487","article-title":"Hijacking of the host ubiquitin network by Legionella pneumophila","volume":"7","author":"J Qiu","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"issue":"7","key":"ppat.1013522.ref005","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/cmi.12450","article-title":"Formation of a pathogen vacuole according to Legionella pneumophila: how to kill one bird with many stones","volume":"17","author":"I Finsel","year":"2015","journal-title":"Cell Microbiol"},{"key":"ppat.1013522.ref006","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mib.2015.11.002","article-title":"Legionella pneumophila, armed to the hilt: justifying the largest arsenal of effectors in the bacterial world","volume":"29","author":"AW Ensminger","year":"2016","journal-title":"Curr Opin Microbiol"},{"issue":"10","key":"ppat.1013522.ref007","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nrmicro.2017.67","article-title":"Legionella and Coxiella effectors: strength in diversity and activity","volume":"15","author":"J Qiu","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1013522.ref008","doi-asserted-by":"crossref","first-page":"790442","DOI":"10.3389\/fmicb.2021.790442","article-title":"Exploitation of the host ubiquitin system: means by Legionella pneumophila","volume":"12","author":"J Luo","year":"2021","journal-title":"Front Microbiol"},{"issue":"12","key":"ppat.1013522.ref009","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000704","article-title":"Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa","volume":"5","author":"CT Price","year":"2009","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013522.ref010","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nchembio.751","article-title":"A Warburg shakeup","volume":"8","author":"C Goodman","year":"2011","journal-title":"Nat Chem Biol"},{"issue":"9","key":"ppat.1013522.ref011","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.1128\/IAI.00344-10","article-title":"E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates","volume":"78","author":"AW Ensminger","year":"2010","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1013522.ref012","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/j.1462-5822.2010.01467.x","article-title":"The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication","volume":"12","author":"M Lomma","year":"2010","journal-title":"Cell Microbiol"},{"issue":"6","key":"ppat.1013522.ref013","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1111\/j.1365-2958.2008.06124.x","article-title":"Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions","volume":"67","author":"T Kubori","year":"2008","journal-title":"Mol Microbiol"},{"issue":"12","key":"ppat.1013522.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001216","article-title":"Legionella metaeffector exploits host proteasome to temporally regulate cognate effector","volume":"6","author":"T Kubori","year":"2010","journal-title":"PLoS Pathog"},{"issue":"42","key":"ppat.1013522.ref015","doi-asserted-by":"crossref","first-page":"25766","DOI":"10.1074\/jbc.M115.637397","article-title":"Host cell-catalyzed S-Palmitoylation mediates Golgi targeting of the Legionella Ubiquitin Ligase GobX","volume":"290","author":"Y-H Lin","year":"2015","journal-title":"Journal of Biological Chemistry"},{"issue":"2","key":"ppat.1013522.ref016","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.str.2016.12.015","article-title":"Structural mimicry by a bacterial F Box Effector Hijacks the Host Ubiquitin-Proteasome System","volume":"25","author":"K Wong","year":"2017","journal-title":"Structure"},{"issue":"4","key":"ppat.1013522.ref017","article-title":"Systematic identification of host cell regulators of Legionella pneumophila pathogenesis using a genome-wide CRISPR screen","volume":"26","author":"EE Jeng","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"6","key":"ppat.1013522.ref018","article-title":"Ubiquitination of Sec22b by a novel Legionella pneumophila ubiquitin E3 ligase","volume":"14","author":"K Ma","year":"2023","journal-title":"mBio"},{"issue":"2","key":"ppat.1013522.ref019","article-title":"RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases","volume":"14","author":"Y-H Lin","year":"2018","journal-title":"PLoS Pathog"},{"key":"ppat.1013522.ref020","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1242\/jcs.041046","article-title":"DUBs at a glance","volume":"122","author":"KD Wilkinson","year":"2009","journal-title":"J Cell Sci"},{"issue":"49","key":"ppat.1013522.ref021","doi-asserted-by":"crossref","first-page":"15090","DOI":"10.1073\/pnas.1514568112","article-title":"Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination","volume":"112","author":"MJ Sheedlo","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"ppat.1013522.ref022","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12840","article-title":"LotA, a Legionella deubiquitinase, has dual catalytic activity and contributes to intracellular growth","volume":"20","author":"T Kubori","year":"2018","journal-title":"Cell Microbiol"},{"issue":"6","key":"ppat.1013522.ref023","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1074\/jbc.RA119.011758","article-title":"The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the Legionella phagosome","volume":"295","author":"K Ma","year":"2020","journal-title":"J Biol Chem"},{"issue":"15","key":"ppat.1013522.ref024","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020105127","article-title":"Identification and characterization of diverse OTU deubiquitinases in bacteria","volume":"39","author":"AF Schubert","year":"2020","journal-title":"EMBO J"},{"key":"ppat.1013522.ref025","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.58277","article-title":"Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection","volume":"9","author":"D Shin","year":"2020","journal-title":"eLife"},{"key":"ppat.1013522.ref026","article-title":"Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes","volume":"9","author":"S Liu","year":"2020","journal-title":"eLife"},{"issue":"5","key":"ppat.1013522.ref027","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/sj.embor.embor824","article-title":"Otubains: a new family of cysteine proteases in the ubiquitin pathway","volume":"4","author":"MY Balakirev","year":"2003","journal-title":"EMBO Rep"},{"issue":"10","key":"ppat.1013522.ref028","doi-asserted-by":"crossref","first-page":"108107","DOI":"10.1016\/j.celrep.2020.108107","article-title":"Legionella manipulates non-canonical SNARE pairing using a bacterial deubiquitinase","volume":"32","author":"T Kitao","year":"2020","journal-title":"Cell Rep"},{"issue":"8","key":"ppat.1013522.ref029","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/s41564-019-0454-1","article-title":"A bacterial effector deubiquitinase specifically hydrolyses linear ubiquitin chains to inhibit host inflammatory signalling","volume":"4","author":"M Wan","year":"2019","journal-title":"Nat Microbiol"},{"key":"ppat.1013522.ref030","doi-asserted-by":"crossref","first-page":"1058751","DOI":"10.3389\/fcell.2022.1058751","article-title":"The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution","volume":"10","author":"M Roman-Trufero","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"ppat.1013522.ref031","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/s41467-020-16211-x","article-title":"Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination","volume":"11","author":"K Puvar","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1013522.ref032","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41564-018-0282-8","article-title":"Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N","volume":"4","author":"N Gan","year":"2019","journal-title":"Nat Microbiol"},{"issue":"2","key":"ppat.1013522.ref033","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.celrep.2018.03.060","article-title":"Discovery of ubiquitin deamidases in the pathogenic arsenal of Legionella pneumophila","volume":"23","author":"D Valleau","year":"2018","journal-title":"Cell Rep"},{"issue":"4","key":"ppat.1013522.ref034","article-title":"Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination","volume":"39","author":"N Gan","year":"2020","journal-title":"EMBO J"},{"issue":"3","key":"ppat.1013522.ref035","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1073\/pnas.0304916101","article-title":"Multiple substrates of the Legionella pneumophila Dot\/Icm system identified by interbacterial protein transfer","volume":"101","author":"Z-Q Luo","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7601","key":"ppat.1013522.ref036","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nature17657","article-title":"Ubiquitination independent of E1 and E2 enzymes by bacterial effectors","volume":"533","author":"J Qiu","year":"2016","journal-title":"Nature"},{"issue":"6","key":"ppat.1013522.ref037","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.cell.2016.11.019","article-title":"Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination","volume":"167","author":"S Bhogaraju","year":"2016","journal-title":"Cell"},{"issue":"2","key":"ppat.1013522.ref038","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.chom.2016.12.007","article-title":"A single Legionella effector catalyzes a multistep ubiquitination pathway to rearrange tubular endoplasmic reticulum for replication","volume":"21","author":"KM Kotewicz","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"3","key":"ppat.1013522.ref039","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009437","article-title":"Legionella hijacks the host Golgi-to-ER retrograde pathway for the association of Legionella-containing vacuole with the ER","volume":"17","author":"M Kawabata","year":"2021","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013522.ref040","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2019.10.019","article-title":"Regulation of phosphoribosyl-linked serine ubiquitination by deubiquitinases DupA and DupB","volume":"77","author":"D Shin","year":"2020","journal-title":"Mol Cell"},{"issue":"47","key":"ppat.1013522.ref041","doi-asserted-by":"crossref","first-page":"23518","DOI":"10.1073\/pnas.1916287116","article-title":"Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain-containing Legionella effectors","volume":"116","author":"M Wan","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7769","key":"ppat.1013522.ref042","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41586-019-1440-8","article-title":"Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin catalysed glutamylation","volume":"572","author":"S Bhogaraju","year":"2019","journal-title":"Nature"},{"issue":"6442","key":"ppat.1013522.ref043","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.aaw7446","article-title":"Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases","volume":"364","author":"MH Black","year":"2019","journal-title":"Science"},{"issue":"7769","key":"ppat.1013522.ref044","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41586-019-1439-1","article-title":"Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase","volume":"572","author":"N Gan","year":"2019","journal-title":"Nature"},{"key":"ppat.1013522.ref045","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.51162","article-title":"Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ","volume":"8","author":"A Sulpizio","year":"2019","journal-title":"Elife"},{"issue":"2","key":"ppat.1013522.ref046","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1128\/IAI.01278-06","article-title":"The Legionella pneumophila effector SidJ is required for efficient recruitment of endoplasmic reticulum proteins to the bacterial phagosome","volume":"75","author":"Y Liu","year":"2007","journal-title":"Infect Immun"},{"issue":"8020","key":"ppat.1013522.ref047","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41586-024-07573-z","article-title":"Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling","volume":"631","author":"T Wang","year":"2024","journal-title":"Nature"},{"issue":"1","key":"ppat.1013522.ref048","doi-asserted-by":"crossref","first-page":"5953","DOI":"10.1038\/s41467-024-50311-2","article-title":"Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms","volume":"15","author":"J Fu","year":"2024","journal-title":"Nat Commun"},{"issue":"6","key":"ppat.1013522.ref049","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1083\/jcb.201112098","article-title":"A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells","volume":"196","author":"KJ Roux","year":"2012","journal-title":"J Cell Biol"},{"issue":"4","key":"ppat.1013522.ref050","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1074\/mcp.O115.051839","article-title":"Enhanced Purification of Ubiquitinated Proteins by Engineered Tandem Hybrid Ubiquitin-binding Domains (ThUBDs)","volume":"15","author":"Y Gao","year":"2016","journal-title":"Mol Cell Proteomics"},{"issue":"12","key":"ppat.1013522.ref051","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1038\/s41596-020-0399-0","article-title":"Proximity labeling in mammalian cells with TurboID and split-TurboID","volume":"15","author":"KF Cho","year":"2020","journal-title":"Nat Protoc"},{"issue":"29","key":"ppat.1013522.ref052","doi-asserted-by":"crossref","first-page":"10538","DOI":"10.1073\/pnas.1402605111","article-title":"The Legionella effector SidC defines a unique family of ubiquitin ligases important for bacterial phagosomal remodeling","volume":"111","author":"F Hsu","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ppat.1013522.ref053","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nrm.2016.91","article-title":"Structural insights into the catalysis and regulation of E3 ubiquitin ligases","volume":"17","author":"L Buetow","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"ppat.1013522.ref054","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/cr.2016.35","article-title":"E2 enzymes: more than just middle men","volume":"26","author":"MD Stewart","year":"2016","journal-title":"Cell Res"},{"key":"ppat.1013522.ref055","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"J S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res"},{"issue":"7873","key":"ppat.1013522.ref056","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"1","key":"ppat.1013522.ref057","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrmicro1967","article-title":"The Legionella pneumophila replication vacuole: making a cosy niche inside host cells","volume":"7","author":"RR Isberg","year":"2008","journal-title":"Nat Rev Microbiol"},{"issue":"5","key":"ppat.1013522.ref058","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1128\/IAI.68.5.2939-2947.2000","article-title":"Intracellular growth of Legionella pneumophila in Dictyostelium discoideum, a system for genetic analysis of host-pathogen interactions","volume":"68","author":"JM Solomon","year":"2000","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1013522.ref059","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-2958.1993.tb01092.x","article-title":"Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila","volume":"7","author":"KH Berger","year":"1993","journal-title":"Mol Microbiol"},{"issue":"4","key":"ppat.1013522.ref060","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1365-2958.1994.tb01317.x","article-title":"Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene","volume":"14","author":"KH Berger","year":"1994","journal-title":"Mol Microbiol"},{"issue":"12","key":"ppat.1013522.ref061","doi-asserted-by":"crossref","DOI":"10.1128\/jb.00324-24","article-title":"Legionella pneumophila, a Rosetta stone to understanding bacterial pathogenesis","volume":"206","author":"KA Romanov","year":"2024","journal-title":"J Bacteriol"},{"issue":"12","key":"ppat.1013522.ref062","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.15252\/embr.201540620","article-title":"Ubiquitin-Activated Interaction Traps (UBAITs) identify E3 ligase binding partners","volume":"16","author":"HF O\u2019Connor","year":"2015","journal-title":"EMBO Rep"},{"key":"ppat.1013522.ref063","doi-asserted-by":"crossref","first-page":"905906","DOI":"10.3389\/fcimb.2022.905906","article-title":"The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases","volume":"12","author":"L Qi","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"12","key":"ppat.1013522.ref064","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1010533","article-title":"Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation","volume":"18","author":"L Farrell","year":"2022","journal-title":"PLoS Genet"},{"key":"ppat.1013522.ref065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13008-016-0016-3","article-title":"The role of cullin 5-containing ubiquitin ligases","volume":"11","author":"F Okumura","year":"2016","journal-title":"Cell Div"},{"issue":"21","key":"ppat.1013522.ref066","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1038\/emboj.2013.209","article-title":"TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes","volume":"32","author":"IR Kelsall","year":"2013","journal-title":"EMBO J"},{"issue":"1","key":"ppat.1013522.ref067","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chom.2019.05.008","article-title":"ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection","volume":"26","author":"R H\u00fcttenhain","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"10","key":"ppat.1013522.ref068","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.4049\/jimmunol.1700184","article-title":"ARIH2 ubiquitinates NLRP3 and negatively regulates NLRP3 inflammasome activation in macrophages","volume":"199","author":"A Kawashima","year":"2017","journal-title":"J Immunol"},{"issue":"10","key":"ppat.1013522.ref069","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.08.010","article-title":"Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection","volume":"29","author":"G Luchetti","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"7680","key":"ppat.1013522.ref070","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature24467","article-title":"Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence","volume":"551","author":"P Li","year":"2017","journal-title":"Nature"},{"issue":"5","key":"ppat.1013522.ref071","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1242\/jcs.183954","article-title":"Ubiquitin chain diversity at a glance","volume":"129","author":"M Akutsu","year":"2016","journal-title":"J Cell Sci"},{"issue":"1","key":"ppat.1013522.ref072","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00018-024-05271-7","article-title":"Legionella effectors SidC\/SdcA ubiquitinate multiple small GTPases and SNARE proteins to promote phagosomal maturation","volume":"81","author":"K Ma","year":"2024","journal-title":"Cell Mol Life Sci"},{"issue":"3","key":"ppat.1013522.ref073","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/j.1365-2958.2006.05407.x","article-title":"The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase","volume":"62","author":"Y Zhang","year":"2006","journal-title":"Mol Microbiol"},{"issue":"4","key":"ppat.1013522.ref074","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005552","article-title":"The Salmonella Effector Protein SopA modulates innate immune responses by targeting TRIM E3 ligase family members","volume":"12","author":"J Kamanova","year":"2016","journal-title":"PLoS Pathog"},{"key":"ppat.1013522.ref075","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.1038\/ncomms6430","article-title":"Bacterial effector modulation of host E3 ligase activity suppresses PAMP-triggered immunity in rice","volume":"5","author":"K Ishikawa","year":"2014","journal-title":"Nat Commun"},{"issue":"33","key":"ppat.1013522.ref076","doi-asserted-by":"crossref","first-page":"13725","DOI":"10.1073\/pnas.0907200106","article-title":"A Legionella type IV effector activates the NF-\u03baB pathway by phosphorylating the I\u03baB family of inhibitors","volume":"106","author":"J Ge","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"8","key":"ppat.1013522.ref077","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/j.1462-5822.2010.01452.x","article-title":"LnaB: a Legionella pneumophila activator of NF-kappaB","volume":"12","author":"VP Losick","year":"2010","journal-title":"Cell Microbiol"},{"key":"ppat.1013522.ref078","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-biochem-060815-014922","article-title":"Ubiquitin ligases: structure, function, and regulation","volume":"86","author":"N Zheng","year":"2017","journal-title":"Annu Rev Biochem"},{"issue":"5","key":"ppat.1013522.ref079","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/s41590-021-00886-5","article-title":"NLRP3 inflammasome in cancer and metabolic diseases","volume":"22","author":"BR Sharma","year":"2021","journal-title":"Nat Immunol"},{"key":"ppat.1013522.ref080","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jare.2023.01.001","article-title":"Canonical and non-canonical functions of NLRP3","volume":"53","author":"T Accogli","year":"2023","journal-title":"J Adv Res"},{"issue":"36","key":"ppat.1013522.ref081","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1073\/pnas.1513509112","article-title":"NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets","volume":"112","author":"C Hu","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ppat.1013522.ref082","doi-asserted-by":"crossref","first-page":"6277","DOI":"10.4049\/jimmunol.1002330","article-title":"An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury","volume":"185","author":"AA Shigeoka","year":"2010","journal-title":"J Immunol"},{"key":"ppat.1013522.ref083","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.ircmb.2022.10.001","article-title":"Legionella and mitochondria, an intriguing relationship","volume":"374","author":"FJ Garc\u00eda-Rodr\u00edguez","year":"2023","journal-title":"Int Rev Cell Mol Biol"},{"issue":"6","key":"ppat.1013522.ref084","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1242\/bio.2012778","article-title":"Identification of the ubiquitin ligase Triad1 as a regulator of endosomal transport","volume":"1","author":"G Hassink","year":"2012","journal-title":"Biol Open"},{"issue":"3","key":"ppat.1013522.ref085","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009341","article-title":"Bacteria make surgical strikes on host ubiquitin signaling","volume":"17","author":"TG Franklin","year":"2021","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1013522.ref086","article-title":"Inhibition of host vacuolar H+-ATPase activity by a Legionella pneumophila Effector","volume":"6","author":"L Xu","year":"2010","journal-title":"PLoS Pathog"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013522","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T17:57:18Z","timestamp":1758218238000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013522"}},"subtitle":[],"editor":[{"given":"Dario S.","family":"Zamboni","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":86,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013522","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1013522","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]}}}