دورية أكاديمية
أعرض في EDS

Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death.

التفاصيل البيبلوغرافية
العنوان: Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death.
المؤلفون: Frank D; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Garnish SE; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Sandow JJ; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Weir A; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Liu L; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Clayer E; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia.; Zentrum für Allergie und Umwelt München (ZAUM), Zentrum München, 80333 Munich, Bayern, Germany., Meza L; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Rashidi M; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Cobbold SA; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Scutts SR; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Doerflinger M; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Anderton H; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Lawlor KE; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia., Lalaoui N; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Kueh AJ; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Eng VV; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia., Ambrose RL; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia., Herold MJ; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Samson AL; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Feltham R; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Murphy JM; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia., Ebert G; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia.; Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, 80802 Munich, Bayern, Germany., Pearson JS; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia.; Department of Microbiology, Monash University, Clayton, VIC 3168, Australia., Vince JE; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, VIC 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3050, Australia.
المصدر: IScience [iScience] 2022 Jun 17; Vol. 25 (7), pp. 104632. Date of Electronic Publication: 2022 Jun 17 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Pathogen recognition and TNF receptors signal via receptor interacting serine/threonine kinase-3 (RIPK3) to cause cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 is not fully understood. Using mass-spectrometry, we identified that RIPK3 is ubiquitylated on K469. The expression of mutant RIPK3 K469R demonstrated that RIPK3 ubiquitylation can limit both RIPK3-mediated apoptosis and necroptosis. The enhanced cell death of overexpressed RIPK3 K469R and activated endogenous RIPK3 correlated with an overall increase in RIPK3 ubiquitylation. Ripk3 K469R/K469R mice challenged with Salmonella displayed enhanced bacterial loads and reduced serum IFNγ. However, Ripk3 K469R/K469R macrophages and dermal fibroblasts were not sensitized to RIPK3-mediated apoptotic or necroptotic signaling suggesting that, in these cells, there is functional redundancy with alternate RIPK3 ubiquitin-modified sites. Consistent with this idea, the mutation of other ubiquitylated RIPK3 residues also increased RIPK3 hyper-ubiquitylation and cell death. Therefore, the targeted ubiquitylation of RIPK3 may act as either a brake or accelerator of RIPK3-dependent killing.
Competing Interests: J.M.M. and A.L.S. contribute to a project developing necroptosis inhibitors in collaboration with Anaxis Pharma.
(© 2022 The Authors.)
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فهرسة مساهمة: Keywords: Cell biology; Molecular biology
تواريخ الأحداث: Date Created: 20220708 Latest Revision: 20220716
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9254354
DOI: 10.1016/j.isci.2022.104632
PMID: 35800780
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2022.104632