RIP1-dependent linear and nonlinear recruitments of caspase-8 and RIP3 respectively to necrosome specify distinct cell death outcomes

Abstract

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/deassembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ∼1000 molecules/cell (mpc), the cell solely undergoes TRADDdependent apoptosis. When RIP1 is above ∼1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>∼46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.

Keywords

necrosome / protein complexes quantification / RIP1 / SWATH-MS / network modeling

References

[1] Aebersold R, Mann M (2016) Mass-spectrometric exploration of proteome structure and function. Nature 537:347–355

[2] Al Shweiki MR, Monchgesang S, Majovsky P, Thieme D, Trutschel D, Hoehenwarter W (2017) Assessment of label-free quantification in discovery proteomics and impact of technological factors and natural variability of protein abundance. J Proteome Res 16:1410–1424

[3] Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK (2008) Quantitative analysis of pathways controlling extrinsic apoptosis in single cells. Mol Cell 30:11–25

[4] Bashor CJ, Patel N, Choubey S, Beyzavi A, Kondev J, Collins JJ, Khalil AS (2019) Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies. Science 364:593–597

[5] Berger SB, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M, Capriotti C, Cook M, Finger J,Hughes-Earle A (2014) Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPINdeficient mice. J Immunol 192:5476–5480

[6] Berghe TV, Linkermann A, Jouan-Lanhouet S, Walczak H ,Vandenabeele P (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15:134–146

[7] Brenner D, Blaser H, Mak TW (2015) Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15:362–374

[8] Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 16:55–65

[9] Chen W, Wu J, Li L, Zhang Z, Ren J, Liang Y, Chen F, Yang C,Zhou Z, Su SS (2015) Ppm1b negatively regulates necroptosis through dephosphorylating Rip3. Nat Cell Biol 17:434–444

[10] Chen WW, Yu H, Fan HB,Zhang CC , Zhang M, Zhang C, Cheng Y, Kong J, Liu CF, Geng D (2012) Rip1 mediates the protection of geldanamycin on neuronal injury induced by oxygen-glucose deprivation combined with zvad in primary cortical neurons. J Neurochem 120:70–77

[11] Cox J, Mann M (2011) Quantitative, high-resolution proteomics for data-driven systems biology. Annu Rev Biochem 80:273–299

[12] Dillon CP, Weinlich R, Rodriguez DA, Cripps JG, Quarato G, Gurung P, Verbist KC, Brewer TL, Llambi F, Gong YN (2014) RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell 157:1189–1202

[13] Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, Herreweghe FV, Vandenabeele P,Bertrand MJM (2017) MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat Cell Biol 19:1237–1247

[14] Duprez L, Bertrand MJ, Vanden Berghe T, Dondelinger Y, Festjens N, Vandenabeele P (2012) Intermediate domain of receptorinteracting protein kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 kinase-dependent apoptosis. J Biol Chem 287:14863–14872

[15] Gillespie DT (1977) Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 81:2340–2361

[16] Han J, Zhong CQ, Zhang DW (2011) Programmed necrosis: backup to and competitor with apoptosis in the immune system. Nat. Immunol. 12:1143–1149

[17] Jaco I, Annibaldi A, Lalaoui N, Wilson R, Tenev T, Laurien L, Kim C, Jamal K, John SW, Liccardi G (2017) MK2 phosphorylates RIPK1 to prevent TNF-induced cell death. Mol. Cell 66:698–710

[18] Kaiser WJ, Daley-Bauer LP, Thapa RJ, Mandal P, Berger SB, Huang C, Sundararajan A, Guo H, Roback L, Speck SH (2014) RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc Natl Acad Sci USA 111:7753–7758

[19] Kitano H (2005) International alliances for quantitative modeling in systems biology. Mol Syst Biol 1:1

[20] Li Y, Zhong CQ, Xu X, Cai S, Wu X, Zhang Y, Chen J, Shi J, Lin S, Han J (2015) Group-DIA: analyzing multiple data-independent acquisition mass spectrometry data files. Nat Methods 12:1105–1106

[21] Ludwig C,Gillet L, Rosenberger G,Amon S, Collins BC, Aebersold R (2018) Data-independent acquisition-based SWATH-MS for quantitative proteomics: a tutorial. Mol Syst Biol 14:e8126

[22] Ma W, Trusina A, El-Samad H, Lim WA, Tang C (2009) Defining network topologies that can achieve biochemical adaptation. Cell 138:760–773

[23] Meng H, Liu Z, Li X, Wang H, Jin T, Wu G, Shan B, Christofferson DE, Qi C, Yu Q, Li Y, Yuan J (2018) Death-domain dimerizationmediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis. Proc Natl Acad Sci USA 115:E2001–E2009

[24] Mompean M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, Wu H, McDermott AE (2018) The structure of the necrosome RIPK1-RIPK3 core, a human hetero-amyloid signaling complex. Cell 173:1244–1253

[25] Nakakuki T, Birtwistle MR, Saeki Y, Yumoto N, Ide K, Nagashima T, Brusch L, Ogunnaike BA, Okada-Hatakeyama M, Kholodenko BN (2010) Ligand-specific c-fos expression emerges from the spatiotemporal control of erbb network dynamics. Cell 141:884–896

[26] Newton K, Wickliffe KE, Dugger DL, Maltzman A, Roose-Girma M, Dohse M, Kőműves L, Webster JD, Dixit VM (2019a) Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature 574:428–431

[27] Newton K, Wickliffe KE, Maltzman A, Dugger DL, Reja R, Zhang Y, Roose-Girma M, Modrusan Z, Sagolla MS, Webster JD, Dixit VM (2019b) Activity of caspase-8 determines plasticity between cell death pathways. Nature 575:679–682

[28] Newton K, Wickliffe KE, Maltzman A, Dugger DL, Strasser A, Pham VC, Lill JR, Roose-Girma M, Warming S, Solon M (2016) RIPK1 inhibits ZBP1-driven necroptosis during development. Nature 540:129–133

[29] Oberst A, Dillon CP, Weinlich R, McCormick L, Fitzgerald P, Pop C, Hakem R, Salvesen GS, Green DR (2011) Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature 471:363–367

[30] Ofengeim D, Yuan J (2013) Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death. Nat Rev Mol Cell Biol 14:727–736

[31] Orozco S, Yatim N, Werner MR, Tran H, Gunja SY, Tait SW, Albert ML, Green DR, Oberst A (2014) RIPK1both positively and negatively regulates RIPK3 oligomerization and necroptosis. Cell Death Differ 21:1511–1521

[32] Remijsen Q, Goossens V, Grootjans S, Van den Haute C, Vanlangenakker N, Dondelinger Y, Roelandt R, Bruggeman I, Goncalves A, Bertrand MJ (2014) Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis. Cell Death Dis 5:e1004

[33] Rickard JA, O’Donnell JA, Evans JM, Lalaoui N, Poh AR, Rogers T, Vince JE, Lawlor KE, Ninnis RL, Anderton H (2014) RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157:1175–1188

[34] Shinohara H, Behar M, Inoue K, Hiroshima M, Yasuda T, Nagashima T, Kimura S, Sanjo H, Maeda S, Yumoto N (2014) Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-kappaB activation. Science 344:760–764

[35] Someda M, Kuroki S, Miyachi H, Tachibana M, Yonehara S (2020) Caspase-8, receptor-interacting protein kinase 1 (ripk1), and ripk3 regulate retinoic acid-induced cell differentiation and necroptosis. Cell Death Differ 27:1539–1553

[36] Suda J, Dara L, Yang L, Aghajan M, Song Y, Kaplowitz N, Liu ZX (2016) Knockdown of RIPK1 markedly exacerbates murine immune-mediated liver injury through massive apoptosis of hepatocytes, independent of necroptosis and inhibition of NF- κB. J Immunol 197:3120–3129

[37] Tummers B, Green DR (2017) Caspase-8: regulating life and death. Immunol Rev 277:76–89

[38] Vanlangenakker N, Bertrand MJ, Bogaert P, Vandenabeele P,Vanden Berghe T (2011) TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis 2:e230

[39] Wang CH, Naik NG, Liao LL, Wei SC, Chao YC (2017) Global screening of antiviral genes that suppress baculovirus transgene expression in mammalian cells. Mol Therapy Methods Clin Dev 6:194–206

[40] Wang L, Du F, Wang X (2008) TNF-α induces two distinct caspase-8 activation pathways. Cell 133:693–703

[41] Wang L, Shi X, Zheng S, Xu S (2020) Selenium deficiency exacerbates lps-induced necroptosis by regulating mir-16-5p targeting pi3k in chicken tracheal tissue. Metallomics 12:562–571

[42] Weinlich R, Green DR (2014) The two faces of receptor interacting protein kinase-1. Mol Cell 56:469–480

[43] Wu H (2013) Higher-order assemblies in a new paradigm of signal transduction. Cell 153:287–292

[44] Xu D, Jin T, Zhu H, Chen H, Ofengeim D, Zou C, Mifflin L, Pan L, Amin P, Li W (2018) TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging. Cell 174:1477–1491

[45] Yang R, Huang B, Zhu Y, Li Y, Liu F, Shi J (2018) Cell typedependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance. Sci Adv 4:5077

[46] Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNFinduced cell death from apoptosis to necrosis. Science 325:332–336

[47] Zheng L, Bidere N, Staudt D, Cubre A, Orenstein J, Chan FK, Lenardo M (2006) Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol 26:3505–3513

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