TBK1-associated adapters TANK and AZI2 protect mice against TNF-induced cell death and severe autoinflammatory diseases

. 2024 Nov 19 ; 15 (1) : 10013. [epub] 20241119

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid39562788

Grantová podpora
21-25251S Grantová Agentura České Republiky (Grant Agency of the Czech Republic)
4420 European Molecular Biology Organization (EMBO)
PRIMUS/20/MED/003 Grantová Agentura, Univerzita Karlova (Charles University Grant Agency)
406322 Grantová Agentura, Univerzita Karlova (Charles University Grant Agency)
Cooperatio Univerzita Karlova v Praze (Charles University)
UNCE/MED/016 Univerzita Karlova v Praze (Charles University)
SVV 260637 Ministerstvo Školství, Mládeže a Tělovýchovy (Ministry of Education, Youth and Sports)
LM2023036 Ministerstvo Školství, Mládeže a Tělovýchovy (Ministry of Education, Youth and Sports)
Programme EXCELES, LX22NPO5102 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
802878 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
Programme EXCELES, LX22NPO5103 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
RVO 68378050 Akademie Věd České Republiky (Academy of Sciences of the Czech Republic)
SFB1403 (414786233) Deutsche Forschungsgemeinschaft (German Research Foundation)
16LW0213 Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)

Odkazy

PubMed 39562788
PubMed Central PMC11576971
DOI 10.1038/s41467-024-54399-4
PII: 10.1038/s41467-024-54399-4
Knihovny.cz E-zdroje

The cytokine TNF can trigger highly proinflammatory RIPK1-dependent cell death. Here, we show that the two adapter proteins, TANK and AZI2, suppress TNF-induced cell death by regulating the activation of TBK1 kinase. Mice lacking either TANK or AZI2 do not show an overt phenotype. Conversely, animals deficient in both adapters are born in a sub-Mendelian ratio and suffer from severe multi-organ inflammation, excessive antibody production, male sterility, and early mortality, which can be rescued by TNFR1 deficiency and significantly improved by expressing a kinase-dead form of RIPK1. Mechanistically, TANK and AZI2 both recruit TBK1 to the TNF receptor signaling complex, but with distinct kinetics due to interaction with different complex components. While TANK binds directly to the adapter NEMO, AZI2 is recruited later via deubiquitinase A20. In summary, our data show that TANK and AZI2 cooperatively sustain TBK1 activity during different stages of TNF receptor assembly to protect against autoinflammation.

Zobrazit více v PubMed

Kupka, S., Reichert, M., Draber, P. & Walczak, H. Formation and removal of poly-ubiquitin chains in the regulation of tumor necrosis factor-induced gene activation and cell death. FEBS J283, 2626–2639 (2016). PubMed

Micheau, O. & Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell114, 181–190 (2003). PubMed

Degterev, A. et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol4, 313–321 (2008). PubMed PMC

Cho, Y. S. et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell137, 1112–1123 (2009). PubMed PMC

He, S. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell137, 1100–1111 (2009). PubMed

Zhang, D. W. et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science325, 332–336 (2009). PubMed

Sun, L. et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell148, 213–227 (2012). PubMed

Cai, Z. et al. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol16, 55–65 (2014). PubMed PMC

Varfolomeev, E. & Vucic, D. RIP1 post-translational modifications. Biochem J479, 929–951 (2022). PubMed

Dondelinger, Y. et al. NF-kappaB-Independent Role of IKKalpha/IKKbeta in Preventing RIPK1 Kinase-Dependent Apoptotic and Necroptotic Cell Death during TNF Signaling. Mol Cell60, 63–76 (2015). PubMed

Geng, J. et al. Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun8, 359 (2017). PubMed PMC

Jaco, I. et al. MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. Mol Cell66, 698–710.e695 (2017). PubMed PMC

Menon, M. B. et al. p38(MAPK)/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat Cell Biol19, 1248–1259 (2017). PubMed

Dondelinger, Y. et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat Cell Biol19, 1237–1247 (2017). PubMed

Kirisako, T. et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J25, 4877–4887 (2006). PubMed PMC

Haas, T. L. et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell36, 831–844 (2009). PubMed

Kanayama, A. et al. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell15, 535–548 (2004). PubMed

Rahighi, S. et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell136, 1098–1109 (2009). PubMed

Draber, P. et al. LUBAC-Recruited CYLD and A20 regulate gene activation and cell death by exerting opposing effects on linear ubiquitin in signaling complexes. Cell Rep13, 2258–2272 (2015). PubMed PMC

Xu, D. et al. TBK1 suppresses RIPK1-Driven apoptosis and inflammation during development and in aging. Cell174, 1477–1491.e19 (2018). PubMed PMC

Clark, K. et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J434, 93–104 (2011). PubMed

Lafont, E. et al. TBK1 and IKKepsilon prevent TNF-induced cell death by RIPK1 phosphorylation. Nat Cell Biol20, 1389–1399 (2018). PubMed PMC

van Loo, G. & Bertrand, M. J. M. Death by TNF: a road to inflammation. Nat Rev Immunol23, 289–303 (2023). PubMed PMC

Bonnard, M. et al. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. EMBO J19, 4976–4985 (2000). PubMed PMC

Eren, R. O., Kaya, G. G., Schwarzer, R. & Pasparakis, M. IKKepsilon and TBK1 prevent RIPK1 dependent and independent inflammation. Nat Commun15, 130 (2024). PubMed PMC

Marchlik, E. et al. Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality. J Leukoc Biol88, 1171–1180 (2010). PubMed

Taft, J. et al. Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death. Cell184, 4447–4463.e20 (2021). PubMed PMC

Sun, Y. et al. Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature615, 158–167 (2023). PubMed PMC

Runde, A. P., Mack, R., S, J. P. & Zhang, J. The role of TBK1 in cancer pathogenesis and anticancer immunity. J Exp Clin Cancer Res41, 135 (2022). PubMed PMC

Wild, P. et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science333, 228–233 (2011). PubMed PMC

Fang, R. et al. MAVS activates TBK1 and IKKepsilon through TRAFs in NEMO dependent and independent manner. PLoS Pathog13, e1006720 (2017). PubMed PMC

Zhang, C. et al. Structural basis of STING binding with and phosphorylation by TBK1. Nature567, 394–398 (2019). PubMed PMC

Kawagoe, T. et al. TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat Immunol10, 965–972 (2009). PubMed PMC

Fukasaka, M. et al. Critical role of AZI2 in GM-CSF-induced dendritic cell differentiation. J Immunol190, 5702–5711 (2013). PubMed

Ma, X. et al. Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation. Proc Natl Acad Sci USA109, 9378–9383 (2012). PubMed PMC

Kishore, N. et al. IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. J Biol Chem277, 13840–13847 (2002). PubMed

Liu, T., Zhang, L., Joo, D. & Sun, S. C. NF-kappaB signaling in inflammation. Signal Transduct Target Ther2, 17023 (2017). PubMed PMC

Ngo, K. A. et al. Dissecting the regulatory strategies of NF-kappaB RelA target genes in the inflammatory response reveals differential transactivation logics. Cell Rep30, 2758–2775.e2756 (2020). PubMed PMC

Karin, M. & Lin, A. NF-kappaB at the crossroads of life and death. Nat Immunol3, 221–227 (2002). PubMed

Le Hir, M. et al. Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. J Exp Med183, 2367–2372 (1996). PubMed PMC

Polykratis, A. et al. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol193, 1539–1543 (2014). PubMed PMC

Cicognani, C. et al. Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis. Arch Intern Med157, 792–796 (1997). PubMed

Moustafa, T. et al. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury. Gastroenterology142, 140–151.e112 (2012). PubMed

Ryzhakov, G. & Randow, F. SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK. EMBO J26, 3180–3190 (2007). PubMed PMC

Chariot, A. et al. Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. J Biol Chem277, 37029–37036 (2002). PubMed

Clark, K., Takeuchi, O., Akira, S. & Cohen, P. The TRAF-associated protein TANK facilitates cross-talk within the IkappaB kinase family during Toll-like receptor signaling. Proc Natl Acad Sci USA108, 17093–17098 (2011). PubMed PMC

Bosanac, I. et al. Ubiquitin binding to A20 ZnF4 is required for modulation of NF-kappaB signaling. Mol Cell40, 548–557 (2010). PubMed

Tokunaga, F. et al. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-kappaB regulation. EMBO J31, 3856–3870 (2012). PubMed PMC

Draberova, H. et al. Systematic analysis of the IL-17 receptor signalosome reveals a robust regulatory feedback loop. EMBO J39, e104202 (2020). PubMed PMC

Chen, Y. G. et al. LUBAC enables tumor-promoting LTbeta receptor signaling by activating canonical NF-kappaB. Cell Death Differ10.1038/s41418-024-01355-w (2024). PubMed PMC

Schweizer, P., Kalhoff, H., Horneff, G., Wahn, V. & Diekmann, L. [Polysaccharide specific humoral immunodeficiency in ectodermal dysplasia. Case report of a boy with two affected brothers]. Klin Padiatr211, 459–461 (1999). PubMed

Doffinger, R. et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet27, 277–285 (2001). PubMed

Fujita, F. et al. Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. Mol Cell Biol23, 7780–7793 (2003). PubMed PMC

Nomura, F., Kawai, T., Nakanishi, K. & Akira, S. NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation. Genes Cells5, 191–202 (2000). PubMed

Goncalves, A. et al. Functional dissection of the TBK1 molecular network. PLoS One6, e23971 (2011). PubMed PMC

Hemmi, H. et al. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med199, 1641–1650 (2004). PubMed PMC

Jin, J. et al. The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-kappaB signaling. Nat Immunol13, 1101–1109 (2012). PubMed PMC

Li, D. et al. RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system. Elife6, e27692 (2017). PubMed PMC

Zilberman-Rudenko, J. et al. Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-kappaB activation and autoinflammatory disease. Proc Natl Acad Sci USA113, 1612–1617 (2016). PubMed PMC

Hsu, H., Xiong, J. & Goeddel, D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell81, 495–504 (1995). PubMed

Pobezinskaya, Y. L. et al. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors. Nat Immunol9, 1047–1054 (2008). PubMed PMC

Ermolaeva, M. A. et al. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol9, 1037–1046 (2008). PubMed

Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature596, 583–589 (2021). PubMed PMC

Shimizu, Y., Taraborrelli, L. & Walczak, H. Linear ubiquitination in immunity. Immunol Rev266, 190–207 (2015). PubMed PMC

Gitlin, A. D. et al. N4BP1 coordinates ubiquitin-dependent crosstalk within the IkappaB kinase family to limit Toll-like receptor signaling and inflammation. Immunity57, 973–986.e977 (2024). PubMed PMC

Gao, T. et al. Myeloid cell TBK1 restricts inflammatory responses. Proc Natl Acad Sci USA119, e2107742119 (2022). PubMed PMC

Labun, K. et al. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res47, W171–W174 (2019). PubMed PMC

Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat Protoc8, 2281–2308 (2013). PubMed PMC

Vorndran, M. R. H. & Roeck, B. F. Inconsistency Masks: Removing the Uncertainty from Input-Pseudo-Label Pairs. arXiv:2401.14387 https://ui.adsabs.harvard.edu/abs/2024arXiv240114387V (2024).

Vorndran, M. R. H. & Roeck, B. F. MichaelVorndran/CellLocator: CellLocator v0.9.2 (v0.9.2). Zenodo. 10.5281/zenodo.13774183 (2024).

Ewels, P., Magnusson, M., Lundin, S. & Kaller, M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics32, 3047–3048 (2016). PubMed PMC

Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods14, 417–419 (2017). PubMed PMC

Soneson, C., Love, M. I. & Robinson, M. D. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res4, 1521 (2015). PubMed PMC

Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol15, 550 (2014). PubMed PMC

Jenickova, I. et al. Efficient allele conversion in mouse zygotes and primary cells based on electroporation of Cre protein. Methods191, 87–94 (2021). PubMed

Kusari, F., Mihola, O., Schimenti, J. C. & Trachtulec, Z. Meiotic epigenetic factor PRDM9 impacts sperm quality of hybrid mice. Reproduction160, 53–64 (2020). PubMed

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...