RIP3是TNFα-诱导性细胞坏死途径的关键调控蛋白
摘要
细胞死亡对于多细胞生物体的发育和自稳平衡起着至关重要的作用。细胞凋亡是生理情况下最主要的程序性细胞死亡方式,而细胞坏死曾被认为是一种被动的意外死亡,但是,最近很多证据表明,细胞坏死也是受到调控的,并参与缺血性心脑血管疾病和神经退行性等疾病的发生。因此,阐明程序性坏死的分子机制和研发有效的抑制剂将为制定有效的治疗策略提供强有力的科学依据。
肿瘤坏死因子TNFα是一个多效性细胞因子,参与调节炎症反应、细胞凋亡和坏死等。我们实验室已经发现Smac/Diablo蛋白的类似物Smac mimetic能诱导TNFα-依赖性细胞凋亡,此途径需要激酶RIPK1的参与。有趣的是,当细胞凋亡受到caspase抑制剂zVAD阻止时,Smac mimetic能诱导一些细胞发生依赖于TNFα和RIPK1的细胞坏死。
我们利用高通量RNAi筛选技术鉴定了RIPK1的同家族蛋白RIP3是调控TNFα-诱导性细胞坏死的关键蛋白,其激酶活性是必不可少的。在受到坏死信号刺激时,一个包含有RIP3和RIPK1的蛋白复合体会被诱导形成。过量表达的激酶死亡突变体会与内源性RIPK1相结合从而抑制细胞坏死途径。我们还发现RIP3只在一些细胞中选择性表达,其表达跟TNFα-诱导性细胞坏死密切相关,但不参与TNFα诱导的细胞凋亡途径。而且,异位表达RIP3使得对TNFα-诱导性细胞坏死有抗性的细胞转变成敏感型细胞。我们还建立了RIP3基因敲除小鼠用于RIP3-依赖性细胞坏死的生理学意义。同样的,RIP3-/-MEF也表现出对TNFα-诱导性细胞坏死的抗性。在雨蛙素诱导的小鼠急性胰腺炎模型中,RIP3基因的敲除显著地减少了胰腺细胞的坏死,有效降低了胰腺组织的损伤。这些发现表明RIP3是TNFα-诱导性细胞坏死途径的关键调控蛋白,并可成为新的药物靶点,为相关疾病的治疗提供新的思路。
此外,我们对20万个化合物进行高通量筛选寻找细胞坏死途径的抑制剂,由此发现超过20个化合物可通过干扰信号途径的不同阶段从而有效的抑制TNFα-诱导性细胞坏死。这些化合物应用前景广泛,对其作用靶点的鉴别将有利于揭示细胞坏死途径中新的调控蛋白,而且在动物疾病模型上的深入研究还将促进有效药物的开发,为相关疾病的治疗提供新的手段。
Cell death is a crucial process for development and tissue homeostasis in multicellular organisms by eliminating unwanted and harmful cells.Apoptosis,a form of programmed cell death,is the principal mechanism by which cells are physiologically removed.In contrast to apoptosis,necrosis was originally described as an accidental and passive form of cell death. However,recent evidences suggest necrosis is also well controlled and programmed,and plays a prominent role in pathological conditions including ischemia and neurodegeneration. Understanding the molecular mechanisms of programmed necrosis and exploring potent inhibitors could lead to powerful therapeutic strategies for these devastating diseases. Tumor necrosis factor(TNF)αis a pleiotropic factor involved in diverse cellular responses, including inflammation,apoptosis and necrosis.Previously,our lab has shown that Smac mimetic,a small molecule mimic of Smac/Diablo protein,induces TNFα-dependent apoptosis in a receptor interacting protein kinase 1(RIPK1)-dependent manner.Interestingly,when apoptosis was bloCked by a pan- caspase inhibitor,z-VAD,cell death phenotype was switched from apoptosis to necrosis in certain cell lines.This Smac mimetic induced necrosis is also TNFαand RIPK1-dependent.
Using the high-throughput RNA interference(RNAi) screening assay,we identified RIP3,a serine-threonine kinase and homolog of RIPK1,as an essential regulator in the TNFα-induced necrosis.Stable expression of shRNA targeting RIP3 blocked necrotic cell death while the cell death phenotype was rescued by introducing a shRNA-resistant wild type form of RIP3,but not a kinase deficient RIP3.Upon necrotic stimuli,a protein complex containing both RIPKI and RIP3 was formed.Overexpression of a kinase-dead form of RIP3 blocked necrosis by sequestering endogenous RIPK1.We also noted that RIP3 was selectively expressed in certain cell lines and the endogenous expression of RIP3 correlates very well with the cellular response to TNFα-induced necrosis.Furthermore,ectopic expression of RIP3 rendered the resistant cells to TNFα-induced necrosis.RIP3 knockout mice were generated to further investigate the physiological functions of RIP3.Consistently,RIP3-/- MEF was resistant to TNFα-induced necrosis.RIP3 knockout mice are devoid from inflammation inflicted tissue damage in an acute pancreatitis model.These findings demonstrate that RIP3 is a key determinant for TNFα-induced necrotic cell death and therefore offers a new drug target for evading necrotic damage.
In addition,we screened a chemical library of 200,000 compounds for the chemical inhibitor of the TNFα-induced necrosis.More than 20 compounds exerted profound inhibition on the TNFα-induced necrosis by interfering with necrosis at different stages of the signaling pathway and provide novel opportunities to develop successful therapies.Further insight into the specific targets of the compounds will uncover novel molecules in the regulation of necrosis.
肿瘤坏死因子TNFα是一个多效性细胞因子,参与调节炎症反应、细胞凋亡和坏死等。我们实验室已经发现Smac/Diablo蛋白的类似物Smac mimetic能诱导TNFα-依赖性细胞凋亡,此途径需要激酶RIPK1的参与。有趣的是,当细胞凋亡受到caspase抑制剂zVAD阻止时,Smac mimetic能诱导一些细胞发生依赖于TNFα和RIPK1的细胞坏死。
我们利用高通量RNAi筛选技术鉴定了RIPK1的同家族蛋白RIP3是调控TNFα-诱导性细胞坏死的关键蛋白,其激酶活性是必不可少的。在受到坏死信号刺激时,一个包含有RIP3和RIPK1的蛋白复合体会被诱导形成。过量表达的激酶死亡突变体会与内源性RIPK1相结合从而抑制细胞坏死途径。我们还发现RIP3只在一些细胞中选择性表达,其表达跟TNFα-诱导性细胞坏死密切相关,但不参与TNFα诱导的细胞凋亡途径。而且,异位表达RIP3使得对TNFα-诱导性细胞坏死有抗性的细胞转变成敏感型细胞。我们还建立了RIP3基因敲除小鼠用于RIP3-依赖性细胞坏死的生理学意义。同样的,RIP3-/-MEF也表现出对TNFα-诱导性细胞坏死的抗性。在雨蛙素诱导的小鼠急性胰腺炎模型中,RIP3基因的敲除显著地减少了胰腺细胞的坏死,有效降低了胰腺组织的损伤。这些发现表明RIP3是TNFα-诱导性细胞坏死途径的关键调控蛋白,并可成为新的药物靶点,为相关疾病的治疗提供新的思路。
此外,我们对20万个化合物进行高通量筛选寻找细胞坏死途径的抑制剂,由此发现超过20个化合物可通过干扰信号途径的不同阶段从而有效的抑制TNFα-诱导性细胞坏死。这些化合物应用前景广泛,对其作用靶点的鉴别将有利于揭示细胞坏死途径中新的调控蛋白,而且在动物疾病模型上的深入研究还将促进有效药物的开发,为相关疾病的治疗提供新的手段。
Cell death is a crucial process for development and tissue homeostasis in multicellular organisms by eliminating unwanted and harmful cells.Apoptosis,a form of programmed cell death,is the principal mechanism by which cells are physiologically removed.In contrast to apoptosis,necrosis was originally described as an accidental and passive form of cell death. However,recent evidences suggest necrosis is also well controlled and programmed,and plays a prominent role in pathological conditions including ischemia and neurodegeneration. Understanding the molecular mechanisms of programmed necrosis and exploring potent inhibitors could lead to powerful therapeutic strategies for these devastating diseases. Tumor necrosis factor(TNF)αis a pleiotropic factor involved in diverse cellular responses, including inflammation,apoptosis and necrosis.Previously,our lab has shown that Smac mimetic,a small molecule mimic of Smac/Diablo protein,induces TNFα-dependent apoptosis in a receptor interacting protein kinase 1(RIPK1)-dependent manner.Interestingly,when apoptosis was bloCked by a pan- caspase inhibitor,z-VAD,cell death phenotype was switched from apoptosis to necrosis in certain cell lines.This Smac mimetic induced necrosis is also TNFαand RIPK1-dependent.
Using the high-throughput RNA interference(RNAi) screening assay,we identified RIP3,a serine-threonine kinase and homolog of RIPK1,as an essential regulator in the TNFα-induced necrosis.Stable expression of shRNA targeting RIP3 blocked necrotic cell death while the cell death phenotype was rescued by introducing a shRNA-resistant wild type form of RIP3,but not a kinase deficient RIP3.Upon necrotic stimuli,a protein complex containing both RIPKI and RIP3 was formed.Overexpression of a kinase-dead form of RIP3 blocked necrosis by sequestering endogenous RIPK1.We also noted that RIP3 was selectively expressed in certain cell lines and the endogenous expression of RIP3 correlates very well with the cellular response to TNFα-induced necrosis.Furthermore,ectopic expression of RIP3 rendered the resistant cells to TNFα-induced necrosis.RIP3 knockout mice were generated to further investigate the physiological functions of RIP3.Consistently,RIP3-/- MEF was resistant to TNFα-induced necrosis.RIP3 knockout mice are devoid from inflammation inflicted tissue damage in an acute pancreatitis model.These findings demonstrate that RIP3 is a key determinant for TNFα-induced necrotic cell death and therefore offers a new drug target for evading necrotic damage.
In addition,we screened a chemical library of 200,000 compounds for the chemical inhibitor of the TNFα-induced necrosis.More than 20 compounds exerted profound inhibition on the TNFα-induced necrosis by interfering with necrosis at different stages of the signaling pathway and provide novel opportunities to develop successful therapies.Further insight into the specific targets of the compounds will uncover novel molecules in the regulation of necrosis.
引文
Abraham,M.C.,Lu,Y.,and Shaham,S.(2007).A morphologically conserved nonapoptotic program promotes linker cell death in Caenorhabditis elegans.Dev Cell 12,73-86.
Ambrosini,G.,Adida,C,and Altieri,D.C.(1997).A novel anti-apoptosis gene,survivin,expressed in cancer and lymphoma.Nat Med 3,917-921.
Ame,J.C.,Spenlehauer,C,and de Murcia,G.(2004).The PARP superfamily.Bioessays 26,882-893.
Ashkenazi,A.(2002).Targeting death and decoy receptors of the tumour-necrosis factor superfamily.Nat Rev Cancer 2,420-430.
Ashkenazi,A.,and Dixit,V.M.(1998).Death receptors:signaling and modulation.Science 281,1305-1308.
Baines,C.P.,Kaiser,R.A.,Purcell,N.H.,Blair,N.S.,Osinska,H.,Hambleton,M.A.,Brunskill,E.W.,Sayen,M.R.,Gottlieb,R.A.,Dorn,G.W.,et al.(2005).Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death.Nature 434,658-662.
Boatright,K.M.,and Salvesen,G.S.(2003).Mechanisms of caspase activation.Curr Opin Cell Biol 15,725-731.
Cauwels,A.,Janssen,B.,Waeytens,A.,Cuvelier,C,and Brouckaert,P.(2003).Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2.Nat Immunol 4,387-393.
Chai,J.,Du,C,Wu,J.W.,Kyin,S.,Wang,X.,and Shi,Y.(2000).Structural and biochemical basis of apoptotic activation by Smac/DIABLO.Nature 406,855-862.
Chai,J.,Shiozaki,E.,Srinivasula,S.M.,Wu,Q.,Datta,P.,Alnemri,E.S.,and Shi,Y.(2001).Structural basis of caspase-7 inhibition by XIAP.Cell 104,769-780.
Chan,F.K.,Shisler,J.,Bixby,J.G.,Felices,M.,Zheng,L.,Appel,M.,Orenstein,J.,Moss,B.,and Lenardo,M.J.(2003).A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.J Biol Chem 278,51613-51621.
Crompton,M.(2003).On the involvement of mitochondrial intermembrane junctional complexes in apoptosis.Curr Med Chem 10,1473-1484.
Crook,N.E.,Clem,R.J.,and Miller,L.K.(1993).An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif.J Virol 67,2168-2174.
D'Amours,D.,Desnoyers,S.,D'Silva,I.,and Poirier,G.G.(1999).Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.Biochem J 342 (Pt 2),249-268.
Degterev,A.,Boyce,M.,and Yuan,J.(2003).A decade of caspases.Oncogene 22,8543-8567.
Degterev,A.,Hitomi,J.,Germscheid,M.,Ch'en,I.L.,Korkina,O.,Teng,X.,Abbott,D.,Cuny,G.D.,Yuan,C,Wagner,G.,et al.(2008).Identification of RIP 1 kinase as a specific cellular target of necrostatins.Nat Chem Biol 4,313-321.
Degterev,A.,Huang,Z.,Boyce,M.,Li,Y.,Jagtap,P.,Mizushima,N.,Cuny,G.D.,Mitchison,T.J.,Moskowitz,M.A.,and Yuan,J.(2005).Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.Nat Chem Biol 1,112-119.
Degterev,A.,and Yuan,J.(2008).Expansion and evolution of cell death programmes.Nat Rev Mol Cell Biol 9,378-390.
Deveraux,Q.L.,Takahashi,R.,Salvesen,G.S.,and Reed,J.C.(1997).X-Iinked IAP is a direct inhibitor of cell-death proteases.Nature 388,300-304.
Du,C,Fang,M.,Li,Y.,Li,L.,and Wang,X.(2000).Smac,a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.Cell 102,33-42.
Feng,S.,Yang,Y.,Mei,Y.,Ma,L.,Zhu,D.E.,Hoti,N.,Castanares,M.,and Wu,M.(2007).
Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain.Cell Signal 19,2056-2067.
Festjens,N.,Vanden Berghe,T.,Cornells,S.,and Vandenabeele,P.(2007).RIP1,a kinase on the crossroads of a cell's decision to live or die.Cell Death Differ 14,400-410.
Festjens,N.,Vanden Berghe,T.,and Vandenabeele,P.(2006).Necrosis,a well-orchestrated form of cell demise:signalling cascades,important mediators and concomitant immune response.Biochim Biophys Acta 1757,1371-1387.
Fiers,W.,Beyaert,R.,Declercq,W.,and Vandenabeele,P.(1999).More than one way to die:apoptosis,necrosis and reactive oxygen damage.Oncogene 18,7719-7730.
Golstein,P.,and Kroemer,G.(2007).Cell death by necrosis:towards a molecular definition.Trends Biochem Sci 32,37-43.
Hakem,R.,Hakem,A.,Duncan,G.S.,Henderson,J.T.,Woo,M.,Soengas,M.S.,Elia,A.,de la Pompa,J.L.,Kagi,D.,Khoo,W.,et al.(1998).Differential requirement for caspase 9 in apoptotic pathways in vivo.Cell 94,339-352.
Hauser,H.P.,Bardroff,M.,Pyrowolakis,G.,and Jentsch,S.(1998).A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors.J Cell Biol 141,1415-1422.
Hinds,M.G.,Norton,R.S.,Vaux,D.L.,and Day,C.L.(1999).Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat.Nat Struct Biol 6,648-651.
Holler,N.,Zaru,R.,Micheau,O.,Thome,M.,Attinger,A.,Valitutti,S.,Bodmer,J.L.,Schneider,P.,Seed,B.,and Tschopp,J.(2000).Fas triggers an alternative,caspase-8-independent cell death pathway using the kinase RIP as effector molecule.Nat Immunol 1,489-495.
Irmler,M.,Thome,M.,Hahne,M.,Schneider,P.,Hofmann,K.,Steiner,V.,Bodmer,J.L.,Schroter,M.,Burns,K.,Mattmann,C,et al.(1997).Inhibition of death receptor signals by cellular FLIP.Nature 388,190-195.
Kasof,G.M.,Prosser,J.C,Liu,D.,Lorenzi,M.V.,and Gomes,B.C.(2000).The RIP-like kinase,RIP3,induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria.FEBS Lett 473,285-291.
Kawahara,A.,Ohsawa,Y.,Matsumura,H.,Uchiyama,Y.,and Nagata,S.(1998).
Caspase-independent cell killing by Fas-associated protein with death domain.J Cell Biol 143,1353-1360.
Kerr,J.F.,Wyllie,A.H.,and Currie,A.R.(1972).Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.Br J Cancer 26,239-257.
Khwaja,A.,and Tatton,L.(1999).Resistance to the cytotoxic effects of tumor necrosis factor alpha can be overcome by inhibition of a FADD/caspase-dependent signaling pathway.J Biol Chem 274,36817-36823.
Kim,Y.S.,Morgan,M.J.,Choksi,S.,and Liu,Z.G.(2007).TNF-induced activation of the Noxl NADPH oxidase and its role in the induction of necrotic cell death.Mol Cell 26,675-687.
Kumar,A.,and Rothman,J.H.(2007).Cell death:hook,line and linker.Curr Biol 17,R286-289.
Latta,M.,Kunstle,G.,Lucas,R.,Hentze,H.,and Wendel,A.(2007).ATP-depleting carbohydrates prevent tumor necrosis factor receptor 1-dependent apoptotic and necrotic liver injury in mice.J Pharmacol Exp Ther 321,875-883.
Levine,B.,and Klionsky,D.J.(2004).Development by self-digestion:molecular mechanisms and biological functions of autophagy.Dev Cell 6,463-477.
Lewis,J.,Devin,A.,Miller,A.,Lin,Y.,Rodriguez,Y.,Neckers,L.,and Liu,Z.G.(2000).
Disruption of hsp90 function results in degradation of the death domain kinase,receptor-interacting protein (RIP),and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation.J Biol Chem 275,10519-10526.
Li,K.,Li,Y.,Shelton,J.M.,Richardson,J.A.,Spencer,E.,Chen,Z.J.,Wang,X.,and Williams,R.S.(2000).Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis.Cell 101,389-399.
Li,L.,Thomas,R.M.,Suzuki,H.,De Brabander,J.K.,Wang,X.,and Harran,P.G.(2004).A small molecule Smac mimic potentiates TRAIL-and TNFalpha-mediated cell death.Science 305,1471-1474.
Li,L.Y.,Luo,X.,and Wang,X.(2001).Endonuclease G is an apoptotic DNase when released from mitochondria.Nature 412,95-99.
Li,P.,Nijhawan,D.,Budihardjo,I.,Srinivasula,S.M.,Ahmad,M.,Alnemri,E.S.,and Wang,X.(1997).Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade.Cell 91,479-489.
Li,Q.,and Verma,I.M.(2002).NF-kappaB regulation in the immune system.Nat Rev Immunol 2,725-734.
Lim,S.Y.,Davidson,S.M.,Mocanu,M.M.,Yellon,D.M.,and Smith,C.C.(2007).The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore.Cardiovasc Drugs Ther 21,467-469.
Lin,T.,and Yang,M.S.(2008).Benzo[a]pyrene-induced necrosis in the HepG(2) cells via PARP-1 activation andNAD(+) depletion.Toxicology 245,147-153.
Lin,Y.,Choksi,S.,Shen,H.M.,Yang,Q.F.,Hur,G.M.,Kim,Y.S.,Tran,J.H.,Nedospasov,S.A.,and Liu,Z.G.(2004).Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation.J Biol Chem 279,10822-10828.
Liston,P.,Roy,N.,Tamai,K.,Lefebvre,C,Baird,S.,Cherton-Horvat,G.,Farahani,R.,McLean,M.,Ikeda,J.E.,MacKenzie,A.,et al.(1996).Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes.Nature 379,349-353.
Liu,X.,Kim,C.N.,Yang,J.,Jemmerson,R.,and Wang,X.(1996).Induction of apoptotic program in cell-free extracts:requirement for dATP and cytochrome c.Cell 86,147-157.
Luo,X.,Budihardjo,I.,Zou,H.,Slaughter,C,and Wang,X.(1998).Bid,a Bcl2 interacting protein,mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.Cell 94,481-490.
Ma,Y.,Temkin,V.,Liu,H.,and Pope,R.M.(2005).NF-kappaB protects macrophages from lipopolysaccharide-induced cell death:the role of caspase 8 and receptor-interacting protein.J Biol Chem 280,41827-41834.
Mareninova,O.A.,Sung,K.F.,Hong,P.,Lugea,A.,Pandol,S.J.,Gukovsky,I.,and Gukovskaya,A.S.(2006).Cell death in pancreatitis:caspases protect from necrotizing pancreatitis.J Biol Chem 281,3370-3381.
Martinon,F.,Burns,K.,and Tschopp,J.(2002).The inflammasome:a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.Mol Cell 10,417-426.
Masutani,M.,Suzuki,H.,Kamada,N.,Watanabe,M.,Ueda,O.,Nozaki,T.,Jishage,K.,Watanabe,T.,Sugimoto,T.,Nakagama,H.,et al.(1999).Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes.Proc Natl Acad Sci U S A 96,2301-2304.
Micheau,O.,Lens,S.,Gaide,O.,Alevizopoulos,K.,and Tschopp,J.(2001).NF-kappaB signals induce the expression of c-FLIP.Mol Cell Biol 21,5299-5305.
Micheau,O.,and Tschopp,J.(2003).Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.Cell 114,181-190.
Miller,L.K.(1999).An exegesis of IAPs:salvation and surprises from BIR motifs.Trends Cell Biol 9,323-328.
Nakagawa,T.,Shimizu,S.,Watanabe,T.,Yamaguchi,O.,Otsu,K.,Yamagata,H.,Inohara,H.,Kubo,T.,and Tsujimoto,Y.(2005).Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death.Nature 434,652-658.
Newton,K.,Sun,X.,and Dixit,V.M.(2004).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 24,1464-1469.
Oei,S.L.,Keil,C,and Ziegler,M.(2005).Poly(ADP-ribosylation) and genomic stability.Biochem Cell Biol 83,263-269.
Petersen,S.L.,Wang,L.,Yalcin-Chin,A.,Li,L.,Peyton,M.,Minna,J.,Harran,P.,and Wang,X.(2007).Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis.Cancer Cell 12,445-456.
Richter,B.W.,Mir,S.S.,Eiben,L.J.,Lewis,J.,Reffey,S.B.,Frattini,A.,Tian,L.,Frank,S.,Youle,R.J.,Nelson,D.L.,et al.(2001).Molecular cloning of ILP-2,a novel member of the inhibitor of apoptosis protein family.Mol Cell Biol 21,4292-4301.
Rothe,M.,Pan,M.G.,Henzel,W.J.,Ayres,T.M.,and Goeddel,D.V.(1995).The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.Cell 83,1243-1252.
Roy,N.,Mahadevan,M.S.,McLean,M.,Shutler,G.,Yaraghi,Z.,Farahani,R.,Baird,S.,Besner-Johnston,A.,Lefebvre,C,Kang,X.,et al.(1995).The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.Cell 80,167-178.
Salvesen,G.S.,and Duckett,C.S.(2002).IAP proteins:blocking the road to death's door.Nat Rev Mol Cell Biol 3,401-410.
Scaffidi,P.,Misteli,T.,and Bianchi,M.E.(2002).Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature 418,191-195.
Schulze-Osthoff,K.,Ferrari,D.,Los,M.,Wesselborg,S.,and Peter,M.E.(1998).Apoptosis signaling by death receptors.Eur J Biochem 254,439-459.
Shimizu,S.,Konishi,A.,Kodama,T.,and Tsujimoto,Y.(2000).BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death.Proc Natl Acad Sci U S A 97,3100-3105.
Shiva,S.,and Darley-Usmar,V.M.(2003).Control of the nitric oxide-cytochrome c oxidase signaling pathway under pathological and physiological conditions.IUBMB Life 55,585-590.
Srinivasula,S.M.,Hegde,R.,Saleh,A.,Datta,P.,Shiozaki,E.,Chai,J.,Lee,R.A.,Robbins,P.D.,Fernandes-Alnemri,T.,Shi,Y.,et al.(2001).A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.Nature 410,112-116.
Stennicke,H.R.,and Salvesen,G.S.(2000).Caspases-controlling intracellular signals by protease zymogen activation.Biochim Biophys Acta 7477,299-306.
Strelow,A.,Bernardo,K.,Adam-Klages,S.,Linke,T.,Sandhoff,K.,Kronke,M.,and Adam,D.(2000).Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death.J Exp Med 192,601-612.
Sun,X.,Lee,J.,Navas,T.,Baldwin,D.T.,Stewart,T.A.,and Dixit,V.M.(1999).RIP3,a novel apoptosis-inducing kinase.J Biol Chem 274,16871-16875.
Sun,X.,Yin,J.,Starovasnik,M.A.,Fairbrother,W.J.,and Dixit,V.M.(2002).Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3.J Biol Chem 277,9505-9511.
Susin,S.A.,Lorenzo,H.K.,Zamzami,N.,Marzo,I.,Snow,B.E.,Brothers,G.M.,Mangion,J.,Jacotot,E.,Costantini,P.,Loeffler,M.,et al.(1999).Molecular characterization of mitochondrial apoptosis-inducing factor.Nature 397,441-446.
Suzuki,Y.,Imai,Y.,Nakayama,H.,Takahashi,K.,Takio,K.,and Takahashi,R.(2001).A serine protease,HtrA2,is released from the mitochondria and interacts with XIAP,inducing cell death.Mol Cell 8,613-621.
Syntichaki,P.,Xu,K.,Driscoll,M.,and Tavernarakis,N.(2002).Specific aspartyl and calpain proteases are required for neurodegeneration in C.elegans.Nature 419,939-944.
Taylor,R.C.,Cullen,S.P.,and Martin,S.J.(2008).Apoptosis:controlled demolition at the cellular level.Nat Rev Mol Cell Biol 9,231-241.
Temkin,V.,Huang,Q.,Liu,H.,Osada,H.,and Pope,R.M.(2006).Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis.Mol Cell Biol 26,2215-2225.
Vanden Berghe,T.,Kalai,M.,van Loo,G.,Declercq,W.,and Vandenabeele,P.(2003).
Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis.J Biol Chem 278,5622-5629.
Ventura,J.J.,Cogswell,P.,Flavell,R.A.,Baldwin,A.S.,Jr.,and Davis,R.J.(2004).JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.Genes Dev 75,2905-2915.
Vercammen,D.,Beyaert,R.,Denecker,G.,Goossens,V.,Van Loo,G.,Declercq,W.,Grooten,J.,Fiers,W.,and Vandenabeele,P.(1998).Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor.J Exp Med 757,1477-1485.
Vercammen,D.,Vandenabeele,P.,Beyaert,R.,Declercq,W.,and Fiers,W.(1997).Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells.Cytokine 9,801-808.
Verhagen,A.M.,Ekert,P.G.,Pakusch,M.,Silke,J.,Connolly,L.M.,Reid,G.E.,Moritz,R.L.,Simpson,R.J.,and Vaux,D.L.(2000).Identification of DIABLO,a mammalian protein that promotes apoptosis by binding to and antagonizing LAP proteins.Cell 102,43-53.
Vitte-Mony,I.,Korneluk,R.G.,and Diaz-Mitoma,F.(1997).Role of XLAP protein,a human member of the inhibitor of apoptosis (LAP) protein family,in phytohemagglutinin-induced apoptosis of human T cell lines.Apoptosis 2,501-509.
Vucic,D.,Stennicke,H.R.,Pisabarro,M.T.,Salvesen,G.S.,and Dixit,V.M.(2000).ML-LAP,a novel inhibitor of apoptosis that is preferentially expressed in human melanomas.Curr Biol 10,1359-1366.
Wang,C.Y.,Mayo,M.W.,Korneluk,R.G.,Goeddel,D.V.,and Baldwin,A.S.,Jr.(1998).
NF-kappaB antiapoptosis:induction of TRAFl and TRAF2 and c-IAPl and C-IAP2 to suppress caspase-8 activation.Science 281,1680-1683.
Wang,L.,Du,F.,and Wang,X.(2008).TNF-alpha induces two distinct caspase-8 activation pathways.Cell 133,693-703.
Wang,X.(2001).The expanding role of mitochondria in apoptosis.Genes Dev 15,2922-2933.
Wu,G.,Chai,J.,Suber,T.L.,Wu,J.W.,Du,C,Wang,X.,and Shi,Y.(2000).Structural basis of LAP recognition by Smac/DIABLO.Nature 408,1008-1012.
Xu,Y.,Huang,S.,Liu,Z.G.,and Han,J.(2006).Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIPl/TRAF2-mediated JNK1 activation.J Biol Chem 281,8788-8795.
Yamashima,T.,Kohda,Y.,Tsuchiya,K.,Ueno,T.,Yamashita,J.,Yoshioka,T.,and Kominami,E.(1998).Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074:a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'.Eur JNeurosci 10,1723-1733.
Yoshida,H.,Kong,Y.Y.,Yoshida,R.,Elia,A.J.,Hakem,A.,Hakem,R.,Penninger,J.M.,and Mak,T.W.(1998).Apafl is required for mitochondrial pathways of apoptosis and brain development.Cell 94,739-750.
Youle,R.J.,and Strasser,A.(2008).The BCL-2 protein family:opposing activities that mediate cell death.Nat Rev Mol Cell Biol 9,47-59.
Yu,L.,Alva,A.,Su,H.,Dutt,P.,Freundt,E.,Welsh,S.,Baehrecke,E.H.,and Lenardo,M.J.(2004).Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8.Science 304,1500-1502.
Yu,P.W.,Huang,B.C.,Shen,M.,Quast,J.,Chan,E.,Xu,X.,Nolan,G.P.,Payan,D.G.,and Luo,Y.(1999).Identification of RIP3,a RIP-like kinase that activates apoptosis and NFkappaB.Curr Biol 9,539-542.
Yuan,J.,Shaham,S.,Ledoux,S.,Ellis,H.M.,and Horvitz,H.R.(1993).The C.elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.Cell 75,641-652.
Zong,W.X.,Ditsworth,D.,Bauer,D.E.,Wang,Z.Q.,and Thompson,C.B.(2004).Alkylating DNA damage stimulates a regulated form of necrotic cell death.Genes Dev 18,1272-1282.
Zou,H.,Henzel,W.J.,Liu,X.,Lutschg,A.,and Wang,X.(1997).Apaf-1,a human protein homologous to C.elegans CED-4,participates in cytochrome c-dependent activation of caspase-3.Cell 90,405-413.
Zou,H.,Li,Y.,Liu,X.,and Wang,X.(1999).An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.J Biol Chem 274,11549-11556.
Ambrosini,G.,Adida,C,and Altieri,D.C.(1997).A novel anti-apoptosis gene,survivin,expressed in cancer and lymphoma.Nat Med 3,917-921.
Ame,J.C.,Spenlehauer,C,and de Murcia,G.(2004).The PARP superfamily.Bioessays 26,882-893.
Ashkenazi,A.(2002).Targeting death and decoy receptors of the tumour-necrosis factor superfamily.Nat Rev Cancer 2,420-430.
Ashkenazi,A.,and Dixit,V.M.(1998).Death receptors:signaling and modulation.Science 281,1305-1308.
Baines,C.P.,Kaiser,R.A.,Purcell,N.H.,Blair,N.S.,Osinska,H.,Hambleton,M.A.,Brunskill,E.W.,Sayen,M.R.,Gottlieb,R.A.,Dorn,G.W.,et al.(2005).Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death.Nature 434,658-662.
Boatright,K.M.,and Salvesen,G.S.(2003).Mechanisms of caspase activation.Curr Opin Cell Biol 15,725-731.
Cauwels,A.,Janssen,B.,Waeytens,A.,Cuvelier,C,and Brouckaert,P.(2003).Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2.Nat Immunol 4,387-393.
Chai,J.,Du,C,Wu,J.W.,Kyin,S.,Wang,X.,and Shi,Y.(2000).Structural and biochemical basis of apoptotic activation by Smac/DIABLO.Nature 406,855-862.
Chai,J.,Shiozaki,E.,Srinivasula,S.M.,Wu,Q.,Datta,P.,Alnemri,E.S.,and Shi,Y.(2001).Structural basis of caspase-7 inhibition by XIAP.Cell 104,769-780.
Chan,F.K.,Shisler,J.,Bixby,J.G.,Felices,M.,Zheng,L.,Appel,M.,Orenstein,J.,Moss,B.,and Lenardo,M.J.(2003).A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.J Biol Chem 278,51613-51621.
Crompton,M.(2003).On the involvement of mitochondrial intermembrane junctional complexes in apoptosis.Curr Med Chem 10,1473-1484.
Crook,N.E.,Clem,R.J.,and Miller,L.K.(1993).An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif.J Virol 67,2168-2174.
D'Amours,D.,Desnoyers,S.,D'Silva,I.,and Poirier,G.G.(1999).Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.Biochem J 342 (Pt 2),249-268.
Degterev,A.,Boyce,M.,and Yuan,J.(2003).A decade of caspases.Oncogene 22,8543-8567.
Degterev,A.,Hitomi,J.,Germscheid,M.,Ch'en,I.L.,Korkina,O.,Teng,X.,Abbott,D.,Cuny,G.D.,Yuan,C,Wagner,G.,et al.(2008).Identification of RIP 1 kinase as a specific cellular target of necrostatins.Nat Chem Biol 4,313-321.
Degterev,A.,Huang,Z.,Boyce,M.,Li,Y.,Jagtap,P.,Mizushima,N.,Cuny,G.D.,Mitchison,T.J.,Moskowitz,M.A.,and Yuan,J.(2005).Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.Nat Chem Biol 1,112-119.
Degterev,A.,and Yuan,J.(2008).Expansion and evolution of cell death programmes.Nat Rev Mol Cell Biol 9,378-390.
Deveraux,Q.L.,Takahashi,R.,Salvesen,G.S.,and Reed,J.C.(1997).X-Iinked IAP is a direct inhibitor of cell-death proteases.Nature 388,300-304.
Du,C,Fang,M.,Li,Y.,Li,L.,and Wang,X.(2000).Smac,a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.Cell 102,33-42.
Feng,S.,Yang,Y.,Mei,Y.,Ma,L.,Zhu,D.E.,Hoti,N.,Castanares,M.,and Wu,M.(2007).
Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain.Cell Signal 19,2056-2067.
Festjens,N.,Vanden Berghe,T.,Cornells,S.,and Vandenabeele,P.(2007).RIP1,a kinase on the crossroads of a cell's decision to live or die.Cell Death Differ 14,400-410.
Festjens,N.,Vanden Berghe,T.,and Vandenabeele,P.(2006).Necrosis,a well-orchestrated form of cell demise:signalling cascades,important mediators and concomitant immune response.Biochim Biophys Acta 1757,1371-1387.
Fiers,W.,Beyaert,R.,Declercq,W.,and Vandenabeele,P.(1999).More than one way to die:apoptosis,necrosis and reactive oxygen damage.Oncogene 18,7719-7730.
Golstein,P.,and Kroemer,G.(2007).Cell death by necrosis:towards a molecular definition.Trends Biochem Sci 32,37-43.
Hakem,R.,Hakem,A.,Duncan,G.S.,Henderson,J.T.,Woo,M.,Soengas,M.S.,Elia,A.,de la Pompa,J.L.,Kagi,D.,Khoo,W.,et al.(1998).Differential requirement for caspase 9 in apoptotic pathways in vivo.Cell 94,339-352.
Hauser,H.P.,Bardroff,M.,Pyrowolakis,G.,and Jentsch,S.(1998).A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors.J Cell Biol 141,1415-1422.
Hinds,M.G.,Norton,R.S.,Vaux,D.L.,and Day,C.L.(1999).Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat.Nat Struct Biol 6,648-651.
Holler,N.,Zaru,R.,Micheau,O.,Thome,M.,Attinger,A.,Valitutti,S.,Bodmer,J.L.,Schneider,P.,Seed,B.,and Tschopp,J.(2000).Fas triggers an alternative,caspase-8-independent cell death pathway using the kinase RIP as effector molecule.Nat Immunol 1,489-495.
Irmler,M.,Thome,M.,Hahne,M.,Schneider,P.,Hofmann,K.,Steiner,V.,Bodmer,J.L.,Schroter,M.,Burns,K.,Mattmann,C,et al.(1997).Inhibition of death receptor signals by cellular FLIP.Nature 388,190-195.
Kasof,G.M.,Prosser,J.C,Liu,D.,Lorenzi,M.V.,and Gomes,B.C.(2000).The RIP-like kinase,RIP3,induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria.FEBS Lett 473,285-291.
Kawahara,A.,Ohsawa,Y.,Matsumura,H.,Uchiyama,Y.,and Nagata,S.(1998).
Caspase-independent cell killing by Fas-associated protein with death domain.J Cell Biol 143,1353-1360.
Kerr,J.F.,Wyllie,A.H.,and Currie,A.R.(1972).Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.Br J Cancer 26,239-257.
Khwaja,A.,and Tatton,L.(1999).Resistance to the cytotoxic effects of tumor necrosis factor alpha can be overcome by inhibition of a FADD/caspase-dependent signaling pathway.J Biol Chem 274,36817-36823.
Kim,Y.S.,Morgan,M.J.,Choksi,S.,and Liu,Z.G.(2007).TNF-induced activation of the Noxl NADPH oxidase and its role in the induction of necrotic cell death.Mol Cell 26,675-687.
Kumar,A.,and Rothman,J.H.(2007).Cell death:hook,line and linker.Curr Biol 17,R286-289.
Latta,M.,Kunstle,G.,Lucas,R.,Hentze,H.,and Wendel,A.(2007).ATP-depleting carbohydrates prevent tumor necrosis factor receptor 1-dependent apoptotic and necrotic liver injury in mice.J Pharmacol Exp Ther 321,875-883.
Levine,B.,and Klionsky,D.J.(2004).Development by self-digestion:molecular mechanisms and biological functions of autophagy.Dev Cell 6,463-477.
Lewis,J.,Devin,A.,Miller,A.,Lin,Y.,Rodriguez,Y.,Neckers,L.,and Liu,Z.G.(2000).
Disruption of hsp90 function results in degradation of the death domain kinase,receptor-interacting protein (RIP),and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation.J Biol Chem 275,10519-10526.
Li,K.,Li,Y.,Shelton,J.M.,Richardson,J.A.,Spencer,E.,Chen,Z.J.,Wang,X.,and Williams,R.S.(2000).Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis.Cell 101,389-399.
Li,L.,Thomas,R.M.,Suzuki,H.,De Brabander,J.K.,Wang,X.,and Harran,P.G.(2004).A small molecule Smac mimic potentiates TRAIL-and TNFalpha-mediated cell death.Science 305,1471-1474.
Li,L.Y.,Luo,X.,and Wang,X.(2001).Endonuclease G is an apoptotic DNase when released from mitochondria.Nature 412,95-99.
Li,P.,Nijhawan,D.,Budihardjo,I.,Srinivasula,S.M.,Ahmad,M.,Alnemri,E.S.,and Wang,X.(1997).Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade.Cell 91,479-489.
Li,Q.,and Verma,I.M.(2002).NF-kappaB regulation in the immune system.Nat Rev Immunol 2,725-734.
Lim,S.Y.,Davidson,S.M.,Mocanu,M.M.,Yellon,D.M.,and Smith,C.C.(2007).The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore.Cardiovasc Drugs Ther 21,467-469.
Lin,T.,and Yang,M.S.(2008).Benzo[a]pyrene-induced necrosis in the HepG(2) cells via PARP-1 activation andNAD(+) depletion.Toxicology 245,147-153.
Lin,Y.,Choksi,S.,Shen,H.M.,Yang,Q.F.,Hur,G.M.,Kim,Y.S.,Tran,J.H.,Nedospasov,S.A.,and Liu,Z.G.(2004).Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation.J Biol Chem 279,10822-10828.
Liston,P.,Roy,N.,Tamai,K.,Lefebvre,C,Baird,S.,Cherton-Horvat,G.,Farahani,R.,McLean,M.,Ikeda,J.E.,MacKenzie,A.,et al.(1996).Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes.Nature 379,349-353.
Liu,X.,Kim,C.N.,Yang,J.,Jemmerson,R.,and Wang,X.(1996).Induction of apoptotic program in cell-free extracts:requirement for dATP and cytochrome c.Cell 86,147-157.
Luo,X.,Budihardjo,I.,Zou,H.,Slaughter,C,and Wang,X.(1998).Bid,a Bcl2 interacting protein,mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.Cell 94,481-490.
Ma,Y.,Temkin,V.,Liu,H.,and Pope,R.M.(2005).NF-kappaB protects macrophages from lipopolysaccharide-induced cell death:the role of caspase 8 and receptor-interacting protein.J Biol Chem 280,41827-41834.
Mareninova,O.A.,Sung,K.F.,Hong,P.,Lugea,A.,Pandol,S.J.,Gukovsky,I.,and Gukovskaya,A.S.(2006).Cell death in pancreatitis:caspases protect from necrotizing pancreatitis.J Biol Chem 281,3370-3381.
Martinon,F.,Burns,K.,and Tschopp,J.(2002).The inflammasome:a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.Mol Cell 10,417-426.
Masutani,M.,Suzuki,H.,Kamada,N.,Watanabe,M.,Ueda,O.,Nozaki,T.,Jishage,K.,Watanabe,T.,Sugimoto,T.,Nakagama,H.,et al.(1999).Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes.Proc Natl Acad Sci U S A 96,2301-2304.
Micheau,O.,Lens,S.,Gaide,O.,Alevizopoulos,K.,and Tschopp,J.(2001).NF-kappaB signals induce the expression of c-FLIP.Mol Cell Biol 21,5299-5305.
Micheau,O.,and Tschopp,J.(2003).Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.Cell 114,181-190.
Miller,L.K.(1999).An exegesis of IAPs:salvation and surprises from BIR motifs.Trends Cell Biol 9,323-328.
Nakagawa,T.,Shimizu,S.,Watanabe,T.,Yamaguchi,O.,Otsu,K.,Yamagata,H.,Inohara,H.,Kubo,T.,and Tsujimoto,Y.(2005).Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death.Nature 434,652-658.
Newton,K.,Sun,X.,and Dixit,V.M.(2004).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 24,1464-1469.
Oei,S.L.,Keil,C,and Ziegler,M.(2005).Poly(ADP-ribosylation) and genomic stability.Biochem Cell Biol 83,263-269.
Petersen,S.L.,Wang,L.,Yalcin-Chin,A.,Li,L.,Peyton,M.,Minna,J.,Harran,P.,and Wang,X.(2007).Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis.Cancer Cell 12,445-456.
Richter,B.W.,Mir,S.S.,Eiben,L.J.,Lewis,J.,Reffey,S.B.,Frattini,A.,Tian,L.,Frank,S.,Youle,R.J.,Nelson,D.L.,et al.(2001).Molecular cloning of ILP-2,a novel member of the inhibitor of apoptosis protein family.Mol Cell Biol 21,4292-4301.
Rothe,M.,Pan,M.G.,Henzel,W.J.,Ayres,T.M.,and Goeddel,D.V.(1995).The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.Cell 83,1243-1252.
Roy,N.,Mahadevan,M.S.,McLean,M.,Shutler,G.,Yaraghi,Z.,Farahani,R.,Baird,S.,Besner-Johnston,A.,Lefebvre,C,Kang,X.,et al.(1995).The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.Cell 80,167-178.
Salvesen,G.S.,and Duckett,C.S.(2002).IAP proteins:blocking the road to death's door.Nat Rev Mol Cell Biol 3,401-410.
Scaffidi,P.,Misteli,T.,and Bianchi,M.E.(2002).Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature 418,191-195.
Schulze-Osthoff,K.,Ferrari,D.,Los,M.,Wesselborg,S.,and Peter,M.E.(1998).Apoptosis signaling by death receptors.Eur J Biochem 254,439-459.
Shimizu,S.,Konishi,A.,Kodama,T.,and Tsujimoto,Y.(2000).BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death.Proc Natl Acad Sci U S A 97,3100-3105.
Shiva,S.,and Darley-Usmar,V.M.(2003).Control of the nitric oxide-cytochrome c oxidase signaling pathway under pathological and physiological conditions.IUBMB Life 55,585-590.
Srinivasula,S.M.,Hegde,R.,Saleh,A.,Datta,P.,Shiozaki,E.,Chai,J.,Lee,R.A.,Robbins,P.D.,Fernandes-Alnemri,T.,Shi,Y.,et al.(2001).A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.Nature 410,112-116.
Stennicke,H.R.,and Salvesen,G.S.(2000).Caspases-controlling intracellular signals by protease zymogen activation.Biochim Biophys Acta 7477,299-306.
Strelow,A.,Bernardo,K.,Adam-Klages,S.,Linke,T.,Sandhoff,K.,Kronke,M.,and Adam,D.(2000).Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death.J Exp Med 192,601-612.
Sun,X.,Lee,J.,Navas,T.,Baldwin,D.T.,Stewart,T.A.,and Dixit,V.M.(1999).RIP3,a novel apoptosis-inducing kinase.J Biol Chem 274,16871-16875.
Sun,X.,Yin,J.,Starovasnik,M.A.,Fairbrother,W.J.,and Dixit,V.M.(2002).Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3.J Biol Chem 277,9505-9511.
Susin,S.A.,Lorenzo,H.K.,Zamzami,N.,Marzo,I.,Snow,B.E.,Brothers,G.M.,Mangion,J.,Jacotot,E.,Costantini,P.,Loeffler,M.,et al.(1999).Molecular characterization of mitochondrial apoptosis-inducing factor.Nature 397,441-446.
Suzuki,Y.,Imai,Y.,Nakayama,H.,Takahashi,K.,Takio,K.,and Takahashi,R.(2001).A serine protease,HtrA2,is released from the mitochondria and interacts with XIAP,inducing cell death.Mol Cell 8,613-621.
Syntichaki,P.,Xu,K.,Driscoll,M.,and Tavernarakis,N.(2002).Specific aspartyl and calpain proteases are required for neurodegeneration in C.elegans.Nature 419,939-944.
Taylor,R.C.,Cullen,S.P.,and Martin,S.J.(2008).Apoptosis:controlled demolition at the cellular level.Nat Rev Mol Cell Biol 9,231-241.
Temkin,V.,Huang,Q.,Liu,H.,Osada,H.,and Pope,R.M.(2006).Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis.Mol Cell Biol 26,2215-2225.
Vanden Berghe,T.,Kalai,M.,van Loo,G.,Declercq,W.,and Vandenabeele,P.(2003).
Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis.J Biol Chem 278,5622-5629.
Ventura,J.J.,Cogswell,P.,Flavell,R.A.,Baldwin,A.S.,Jr.,and Davis,R.J.(2004).JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.Genes Dev 75,2905-2915.
Vercammen,D.,Beyaert,R.,Denecker,G.,Goossens,V.,Van Loo,G.,Declercq,W.,Grooten,J.,Fiers,W.,and Vandenabeele,P.(1998).Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor.J Exp Med 757,1477-1485.
Vercammen,D.,Vandenabeele,P.,Beyaert,R.,Declercq,W.,and Fiers,W.(1997).Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells.Cytokine 9,801-808.
Verhagen,A.M.,Ekert,P.G.,Pakusch,M.,Silke,J.,Connolly,L.M.,Reid,G.E.,Moritz,R.L.,Simpson,R.J.,and Vaux,D.L.(2000).Identification of DIABLO,a mammalian protein that promotes apoptosis by binding to and antagonizing LAP proteins.Cell 102,43-53.
Vitte-Mony,I.,Korneluk,R.G.,and Diaz-Mitoma,F.(1997).Role of XLAP protein,a human member of the inhibitor of apoptosis (LAP) protein family,in phytohemagglutinin-induced apoptosis of human T cell lines.Apoptosis 2,501-509.
Vucic,D.,Stennicke,H.R.,Pisabarro,M.T.,Salvesen,G.S.,and Dixit,V.M.(2000).ML-LAP,a novel inhibitor of apoptosis that is preferentially expressed in human melanomas.Curr Biol 10,1359-1366.
Wang,C.Y.,Mayo,M.W.,Korneluk,R.G.,Goeddel,D.V.,and Baldwin,A.S.,Jr.(1998).
NF-kappaB antiapoptosis:induction of TRAFl and TRAF2 and c-IAPl and C-IAP2 to suppress caspase-8 activation.Science 281,1680-1683.
Wang,L.,Du,F.,and Wang,X.(2008).TNF-alpha induces two distinct caspase-8 activation pathways.Cell 133,693-703.
Wang,X.(2001).The expanding role of mitochondria in apoptosis.Genes Dev 15,2922-2933.
Wu,G.,Chai,J.,Suber,T.L.,Wu,J.W.,Du,C,Wang,X.,and Shi,Y.(2000).Structural basis of LAP recognition by Smac/DIABLO.Nature 408,1008-1012.
Xu,Y.,Huang,S.,Liu,Z.G.,and Han,J.(2006).Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIPl/TRAF2-mediated JNK1 activation.J Biol Chem 281,8788-8795.
Yamashima,T.,Kohda,Y.,Tsuchiya,K.,Ueno,T.,Yamashita,J.,Yoshioka,T.,and Kominami,E.(1998).Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074:a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'.Eur JNeurosci 10,1723-1733.
Yoshida,H.,Kong,Y.Y.,Yoshida,R.,Elia,A.J.,Hakem,A.,Hakem,R.,Penninger,J.M.,and Mak,T.W.(1998).Apafl is required for mitochondrial pathways of apoptosis and brain development.Cell 94,739-750.
Youle,R.J.,and Strasser,A.(2008).The BCL-2 protein family:opposing activities that mediate cell death.Nat Rev Mol Cell Biol 9,47-59.
Yu,L.,Alva,A.,Su,H.,Dutt,P.,Freundt,E.,Welsh,S.,Baehrecke,E.H.,and Lenardo,M.J.(2004).Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8.Science 304,1500-1502.
Yu,P.W.,Huang,B.C.,Shen,M.,Quast,J.,Chan,E.,Xu,X.,Nolan,G.P.,Payan,D.G.,and Luo,Y.(1999).Identification of RIP3,a RIP-like kinase that activates apoptosis and NFkappaB.Curr Biol 9,539-542.
Yuan,J.,Shaham,S.,Ledoux,S.,Ellis,H.M.,and Horvitz,H.R.(1993).The C.elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.Cell 75,641-652.
Zong,W.X.,Ditsworth,D.,Bauer,D.E.,Wang,Z.Q.,and Thompson,C.B.(2004).Alkylating DNA damage stimulates a regulated form of necrotic cell death.Genes Dev 18,1272-1282.
Zou,H.,Henzel,W.J.,Liu,X.,Lutschg,A.,and Wang,X.(1997).Apaf-1,a human protein homologous to C.elegans CED-4,participates in cytochrome c-dependent activation of caspase-3.Cell 90,405-413.
Zou,H.,Li,Y.,Liu,X.,and Wang,X.(1999).An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.J Biol Chem 274,11549-11556.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |