본문 바로가기
KERD
논문KCI 등재

Receptor Interacting Protein 3 Kinase Regulates Caspase-independent Programmed Necrosis

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Programmed necrosis is a specialized cell death that is distinct from apoptosis in morphology and mechanism. Unlike apoptosis, caspases are not required in programmed necrosis. In fact, programmed necrosis occurs optimally when caspases are inactivated, such as infections with viruses that encode caspase inhibitors. Thus, programmed necrosis may be an important anti-viral host defense strategy. The serine/threonine kinase receptor interacting protein1 (RIP1/RIPK1) plays an essential role in programmed necrosis and other caspase-independent cell death programs. However, the molecular basis by which RIP1 mediates caspase independent cell death is poorly understood. Here, we show that the kinase activity of RIP1 is induced in a cytoplasmic signaling complex termed Complex II during tumor necrosis factor alpha (TNF)- induced programmed necrosis. Using a RNA interference (RNAi) screen, we identified RIP3 as a crucial downstream regulator for RIP1-mediated programmed necrosis. RIP3 binds to Complex II and undergoes phosphorylation in a RIP1-dependent manner. RIP3 triggers programmed necrosis by regulating downstream reactive oxygen species (ROS) production. Our results provide significant mechanistic insight on the molecular regulation of TNF-induced programmed necrosis and reveal a physiological clue for RIP3-dependent programmed necrosis in a range of biological events.

Abstract

Programmed necrosis is a specialized cell death that is distinct from apoptosis in morphology and mechanism. Unlike apoptosis, caspases are not required in programmed necrosis. In fact, programmed necrosis occurs optimally when caspases are inactivated, such as infections with viruses that encode caspase inhibitors. Thus, programmed necrosis may be an important anti-viral host defense strategy. The serine/threonine kinase receptor interacting protein1 (RIP1/RIPK1) plays an essential role in programmed necrosis and other caspase-independent cell death programs. However, the molecular basis by which RIP1 mediates caspase independent cell death is poorly understood. Here, we show that the kinase activity of RIP1 is induced in a cytoplasmic signaling complex termed Complex II during tumor necrosis factor alpha (TNF)- induced programmed necrosis. Using a RNA interference (RNAi) screen, we identified RIP3 as a crucial downstream regulator for RIP1-mediated programmed necrosis. RIP3 binds to Complex II and undergoes phosphorylation in a RIP1-dependent manner. RIP3 triggers programmed necrosis by regulating downstream reactive oxygen species (ROS) production. Our results provide significant mechanistic insight on the molecular regulation of TNF-induced programmed necrosis and reveal a physiological clue for RIP3-dependent programmed necrosis in a range of biological events.

참고문헌 (37)

  1. Degterev A, "Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury", Nat Chem Biol, 1, pp.112~119 (2005)
  2. Golstein P, "Cell death by necrosis : towards a molecular definition", Trends Biochem Sci, 32, pp.37~43 (2007)
  3. Festjens N, "Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response", Biochim Biophys Acta, 1757, pp.1371~1387 (2006)
  4. Zong WX, "Necrotic death as a cell fate", Genes Dev, 20, pp.1~15 (2006)
  5. 조영식, "Physiological Consequences of Programmed Necrosis, an Alternative form of Cell Demise", Molecules and Cells, 29(4), pp.327~332 (2010), 한국분자세포생물학회
  6. Wu W, "Necroptosis: an emerging form of programmed cell death", Crit Rev Oncol Hematol, 82, pp.249~258 (2012)
  7. Kono H, "How dying cells alert the immune system to danger", Nat Rev Immunol, 8, pp.279~289 (2008)
  8. Mareninova OA, "Cell death in pancreatitis: caspases protect from necrotizing pancreatitis", J Biol Chem, 281, pp.3370~3381 (2006)
  9. Cauwels A, "Caspase inhibition causes hyperacute tumor necrosis factorinduced shock via oxidative stress and phospholipase A2", Nat Immunol, 4, pp.387~393 (2003)
  10. Smith CC, "Necrostatin: a potentially novel cardioprotective agent?", Cardiovasc Drugs Ther, 21, pp.227~233 (2007)
  11. Chan FK, "A role for tumor necrosis factor receptor-2 and receptorinteracting protein in programmed necrosis and antiviral responses", J Biol Chem, 278, pp.51613~51621 (2003)
  12. Upton JW, "Cytomegalovirus M45 cell death suppression requires receptor-interacting protein(RIP)homotypic interaction motif(RHIM)-dependent interaction with RIP1", J Biol Chem, 283, pp.16966~16970 (2008)
  13. Holler N, "Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule", Nat Immunol, 1, pp.489~495 (2000)
  14. Lin Y, "Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation", J Biol Chem, 279, pp.10822~10828 (2004)
  15. Micheau O, "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes", Cell, 114, pp.181~190 (2003)
  16. Benedict CA, "To kill or be killed : viral evasion of apoptosis", Nat Immunol, 3, pp.1013~1018 (2002)
  17. Li M, "Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells", J Virol, 74, pp.7470~7477 (2000)
  18. Festjens N, "RIP1, a kinase on the crossroads of a cell’s decision to live or die", Cell Death Differ, 14, pp.400~410 (2007)
  19. He S, "Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha", Cell, 137, pp.1100~1111 (2009)
  20. Cho YS, "Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation", Cell, 137, pp.1112~1123 (2009)
  21. Sun X, "Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein(RIP)by RIP3", J Biol Chem, 277, pp.9505~9511 (2002)
  22. Zheng L, "Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1", Mol Cell Biol, 26, pp.3505~3513 (2006)
  23. Lin Y, "Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis", Genes Dev, 13, pp.2514~2526 (1999)
  24. Yu L, "Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8", Science, 304, pp.1500~1502 (2004)
  25. Liu Z, "Reactive oxygen species regulate autophagy through redox-sensitive proteases", Dev Cell, 12, pp.484~485 (2007)
  26. Meylan E, "RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation", Nat Immunol, 5, pp.503~507 (2004)
  27. Sun X, "RIP3, a novel apoptosis-inducing kinase", J Biol Chem, 274, pp.16871~16875 (1999)
  28. Kasof GM, "The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria", FEBS Lett, 473, pp.285~291 (2000)
  29. Newton K, "Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4", Mol Cell Biol, 24, pp.1464~1469 (2004)
  30. Park S, "Shikonin induces programmed necrosislike cell death through the formation of receptor interacting protein 1 and 3 complex", Food Chem Toxicol, 55, pp.36~41 (2013)
  31. Bera AK, "Mitochondrial VDAC can be phosphorylated by cyclic AMP-dependent protein kinase", Biochem Biophys Res Commun, 209, pp.213~217 (1995)
  32. Le Mellay V, "Negative regulation of mitochondrial VDAC channels by C-Raf kinase", BMC Cell Biol, 3, pp.14~ (2002)
  33. Kim YS, "TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death", Mol Cell, 26, pp.675~687 (2007)
  34. Rock KL, "Natural endogenous adjuvants", Springer Semin Immunopathol, 26, pp.231~246 (2005)
  35. Adams S, "Regulation of NFkappaB activity and keratinocyte differentiation by the RIP4protein : implications for cutaneous wound repair", J Invest Dermatol, 127, pp.538~544 (2007)
  36. Coussens LM, "Inflammation and cancer", Nature, 420, pp.860~867 (2002)
  37. Sambhi SK, "Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo", Proc Natl Acad Sci USA, 88, pp.4025~4029 (1991)

관련 논문AI추천

이 간행물의 다른 논문 (8건)