Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press1410.17650/1726-9784-2015-14-2-23-30REVIEWSОБЗОРЫ ЛИТЕРАТУРЫSTRUCTURE AND FUNCTIONS OF MAIN APOPTOSIS RECEPTORS AND LIGANDSСТРУКТУРА И СВОЙСТВА ОСНОВНЫХ РЕЦЕПТОРОВ И ЛИГАНДОВ ВНЕШНЕГО ПУТИ АПОПТОЗАMisyurinV. A.МисюринВсеволод Андреевич
Russian Federation
vsevolod.misYurin@gmail.comФГБНУ «РОНЦ им. Н.Н. Блохина»30062015142233010042018https://bioterapevt.abvpress.ru/jour/article/view/14

Apoptosis can be triggered from external signals. Several homologous receptors transmit apoptotic signals from outside into the cell. For successful activation of apoptosis receptors should interact with their ligands. For example, FAS receptor must bind with FAS-ligand, TNFR1 with TNFα, TRAIL-R1 and TRAIL-R2 with TRAIL, DR3 - with TL1A, respectively. In majority of cases ligands should be anchoring in the cell membrane to perform their functions. FAS and TNFR1 receptors trigger apoptosis only when they are internalized into the cell’s cytoplasm. If FAS and TNFR1 are not internalized, then anti-apoptotic program won’t start. In contrast, TRAIL-R1, TRAIL-R2 and DR3 aren’t internalized during apoptotic signal transduction. Other receptors, TNFR2, TRAIL-R3 and TRAIL-R4 start an anti-apoptotic program. The apoptotic signal starts when DISC complex is formed on the inner side of the cell membrane. FADD, procaspase-8 and intracellular domain of receptor form together DISC complex. If the DISC complex wasn’t formed, signal is transmitted by the NFкB-way via MAP-kinase cascade. In such conditions anti-apoptotic program starts. A variety of receptors and ligands provides for multiple biological functions. For example, receptor-mediated apoptosis takes a part in elimination of infected or transformed cells, regulation of inflammation, modulation of ontogenesis, hematopoiesis and antibody production.

FASTNFoiTRAILTL1AапоптозFASTNFαTRAILTL1AapoptosisБарышников А.Ю. Программируемая клеточная смерть (апоптоз) // Клиническая онкогематология. Фундаментальные исследования и клиническая практика. - 2001. - С. 36.Барышников А.Ю., Шишкин Ю.В. FAS/APO-1 антиген - молекула, опосредующая апоптоз // Гематология и трансфузиология. - 1995. - № 6. - С. 35.Барышников А.Ю., Шишкин Ю.В. Программированная клеточная смерть (апоптоз) // Российский онкологический журнал. - 1996. - № 1. - С. 58.Карапетян В.Л., Степанова Е.В., Барышников А.Ю., Никогосян С.О., Кузнецов В.В. Экспрессия маркеров апоптоза (Р53, BCL-2, BAX) и их прогностическое значение при эпителиальных новообразованиях яичников ранних стадий // Российский биотерапевтический журнал. - 2011. - Т. 10, № 2. - С. 45-9.Короленкова Л.И., Степанова Е.В., Барышников А.Ю. Молекулярно-биологические маркеры пролиферации и апоптоза, как факторы прогрессии цервикальных интраэпителиальных неоплазий и рака шейки матки // Российский биотерапевтический журнал. - 2010. - Т. 9, № 4. - С. 11-6.Кохно А.В., Савченко В.Г., Паровичникова Е.Н. и др. Апоптоз и пролиферативная активность клеток костного мозга у больных апластическими синдромами по данным трепанобиопсии // Терапевтический архив. - 2001. -№ 7. - С. 51.Тагиров О.Т., Кравченко Г.А., Козлов А.Ю. и др. Растворимый FAS(CD95) белок, ингибирующий апоптоз как прогностический биомаркер течения рака молочной железы // Вестник Нижегородского университета им. Н.И. Лобачевского. Серия: Биология. - 2001. - № 1. С. - 21-5.Уткин О.В., Сахарнов Н.А., Преснякова Н.Б. и др. Экспрессия СD95/Fas в клетках крови при раке толстой кишки // Российский биотерапевтический журнал. - 2013. - Т. 12, № 1. - С. 23-9.Adam D., Wiegmann K., Adam-Klages S. et al. A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway // J. Biol. Chem. - 1996. - 271. - P. 14617-22.Aggarwal B.B. Signalling pathways of the TNF superfamily: a double-edged sword // Nature Reviews Immunology. - 2003. - 3(9). - P. 745-56.Baryshnikov A.Y., Zabotina T.N., Sedyakhina N.P. et al. The coexpression of cd34-antigen of early hemopoietic precursors and FAS/APO-1 (CD95)-antigen mediating apoptosis // Experimental Oncology. - 1994. - 16. - P. 343.Black R.A., Rauch C.T., Kozlosky C.J. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells // Nature. - 1997. - 385. - P. 729-33.Blott E.J., Bossi G., Clark R. et al. Fas ligand is targeted to secretory lysosomes via a proline-rich domain in its cytoplasmic tail // J. Cell Sci. - 2001. - 114. - P. 2405-16.Bodmer J.L., Burns K., Schneider P. et al. TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95) // Immunity. - 1997. - 6. - P. 79-88.Bradley J.R. TNF-mediated inflammatory disease // J Pathol. - 2008. - 214(2). - P. 149-60.Chakrabandhu K., Huault S., Garmy N. et al. The extracellular glycosphingolipid-binding motif of Fas defines its internalization route, mode and outcome of signals upon activation by ligand // Cell Death Differ. - 2008. - 15. - P. 182437.Cheng J., Liu C., Koopman W.J., Mountz J.D. Characterization of human Fas gene. Exon/intron organization and promoter region // J. Immunol. - 1995. - 154. - P. 1239-45.Condorelli G., Vigliotta G., Cafieri A. PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis // Oncogene. - 1999. - 18(31). - P. 4409-15.Dembic Z., Loetscher H., Gubler U. et al. Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences // Cytokine. - 1990. - 2. - P. 231-7.Ea C.K., Deng L., Xia Z.P., Pineda G., Chen Z.J. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO // Mol. Cell. - 2006. - 22. - P. 245-57.Edmond V., Dufour F., Poiroux G. et al. Downregulation of ceramide synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell motility // Oncogene. - 2014 doi: 10.1038/onc.2014.55. [Epub ahead of print]Falschlehner C., Ganten T.M., Koschny R. et al. TRAIL and other TRAIL receptor agonists as novel cancer therapeutics // Adv. Exp. Med. Biol. - 2009. - 647. - P. 195-206.Huang B., Eberstadt M., Olejniczak E.T. NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain // Nature. - 1996. - 384(6610). - P. 638-41.Irmler M., Thome M., Hahne M. Inhibition of death receptor signals by cellular FLIP // Nature. - 1997. - 388(6638). -P. 190-5.Janssen O., Qian J., Linkermann A., Kabelitz D. CD95 ligand - Death factor and costimulatory molecule? // Cell Death Differ. - 2003. - 10. - P. 1215-25.Ji W., Li Y., Wan T. et al. Both internalization and AIP1 association are required for tumor necrosis factor receptor 2-mediated JNK signaling // Arteriosclerosis, Thrombosis, and Vascular Biology. - 2012. - 32(9). - P. 2271-9.Kelliher M.A., Grimm S., Ishida Y. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal // Immunity. - 1998. - 8(3). - P. 297-303.Kischkel F.C., Hellbardt S., Behrmann I. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor // EMBO J. - 1995. - 14(22). - P. 5579-88.Kohlhaas S.L., Craxton A., Sun X.M. et al. Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis // J. Biol. Chem. - 2007. - 282. - P. 12831-41.LeBlanc H.N., Ashkenazi A. Apo2L/TRAIL and its death and decoy receptors // Cell Death Differ. - 2003. - 10(1). - P. 66-75.Li H., Kobayashi M., Blonska M., You Y., Lin X. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation // J. Biol. Chem. - 2006. - 281. - P. 13636-43.Malleter M., Tauzin S., Bessede A. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triplenegative breast cancer // Cancer Res. - 2013. - 73(22). - P. 6711-21.Marsters S.A., Sheridan J.P., Donahue C.J. et al. Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa Β // Curr. Biol. - 1996. - 6. - P. 1669-76.McCarthy E.F. The Toxins of William Β. Coley and the Treatment of Bone and Soft-Tissue Sarcomas // Iowa Orthop J. - 2006. - 26. - P. 154-8.Meylan F., Richard A.C., Siegel R.M. TL1A and DR3, a TNF family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation // Immunol Rev. - 2011. - 244(1). - P. 188-96.Micheau O., Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. - 2003. - 114. - P. 181-90.Migone T.S., Zhang J., Luo X. et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator // Immunity. - 2002. - 16. - P. 479-92.Mitsiades N., Yu W.H., Poulaki V. et al. Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity // Cancer Res. - 2001. - 61. - P. 577-81.Moreno E., Yan M., Basler K. Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily // Curr Biol. - 2002. - 12(14). - P. 1263-8.Old L.J. Tumor necrosis factor (TNF) // Science. - 1985. - 230(4726). - P. 630-2.Pan G., O’Rourke K., Chinnaiyan A.M. et al. The receptor for the cytotoxic ligand TRAIL // Science. - 1997. - 276. -P. 111-3.Parlato S., Giammarioli A.M., Logozzi M. et al. CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: A novel regulatory mechanism of the CD95 apoptotic pathway // EMBO J. - 2000. - 19. - P. 5123-34.Peter M.E., Krammer P.H. The CD95(APO-1/Fas) DISC and beyond // Cell Death Differ. - 2003. - 10. - P. 26-35.Polosukhina E.R., Baryshnikov A.Yu., Shishkin Yu.V. et al. Expression of antigen CD95(FAS/APO-1) mediating apoptosis in hemoblastoses using monoclonal antibodies ICO-160 // Гематология и трансфузиология. - 2000. - 45(4). - P. 3-6.Ptisyna Y.S., Bornyakova L.A., Baryshnikov A.Y. et al. A soluble form of FAS/APO-1 (CD95) antigen in the serum of viral hepatitis patients // International Journal on Immunorehabilitation. - 1999. - 14. - P. 110.Rothe M., Sarma V., Dixit V.M., Goeddel D.V. TRAF2-Mediated activation of NFkB by TNF receptor 2 and CD40 // Science. - 1995. - 269(5229). - P. 1424-7.Sakahira H., Enari M., Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis // Nature. - 1998. - 391(6662). - P. 96-9.Sato T., Irie S., Kitada S., Reed J.C. FAP-1: a protein tyrosine phosphatase that associates with Fas // Science. - 1995. -268(5209). - P. 411-5.Scaffidi C., Fulda S., Srinivasan A. Two CD95 (APO-1/Fas) signaling pathways // EMBO J. - 1998. - 17(6). - P. 1675 87.Schneider P., Bodmer J.L., Holler N. et al. Characterization of Fas (Apo-1, CD95)-Fas ligand interaction // J Biol Chem. - 1997. - 272(30). - P. 18827-33.Schneider-Brachert W., Tchikov V., Neumeyer J. et al. Compartmentalization of TNF receptor 1 signaling: Internalized TNF receptosomes as death signaling vesicles // Immunity. - 2004. - 21. - P. 415-28.Screaton G.R., Xu X.N., Olsen A.L. et al. LARD: A new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing // Proc. Natl. Acad. Sci. USA. - 1997. - 94. - P. 4615-9.Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family // Cell. - 1993. - 75(6). - P. 1169-78.Takahashi T., Tanaka M., Inazawa J. et al. Human Fas ligand: Gene structure, chromosomal location and species specificity // Int. Immunol. - 1994. - 6. - P. 1567-74.Tang G., Minemoto Y., Dibling B. et al. Inhibition of JNK activation through NF-kappaB target genes // Nature. - 2001. - 414. - P. 313-7.Tang P., Hung M.C., Klostergaard J. Human pro-tumor necrosis factor is a homotrimer // Biochemistry. - 1996. - 35. -P. 8216-25.Tartaglia L.A., Goeddel D.V., Reynolds C. et al. Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor // Journal of Immunology. - 1993. - 151(9). - P. 4637-41.Tartaglia L.A., Weber R.F., Figari I.S. et al. The two different receptors for tumor necrosis factor mediate distinct cellular responses // Proceedings of the National Academy of Sciences of the United States of America. - 1991. - 88(20). -P. 9292-6.Trauth B.C., Klas C., Peters A.M. et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis // Science. - 1989. - 245(4915). - P. 301-5.Wajant H., Pfizenmaier K., Scheurich P. Tumor necrosis factor signaling // Cell Death Differ. - 2003. - 10. - P. 45-65.Walczak H., Degli-Esposti M.A., Johnson R.S. et al. TRAIL-R2: A novel apoptosis-mediating receptor for TRAIL // EMBO J. - 1997. - 16. - P. 5386-97.Wang L., Yang J.K., Kabaleeswaran V. et al. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations // Nat Struct Mol Biol. - 2010. - 17(11). - P. 1324-9.Wen L., Zhuang L., Luo X., Wei P. TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells // J. Biol. Chem. - 2003. - 278. - P. 39251-8.Wiley S.R., Schooley K., Smolak P.J. et al. Identification and characterization of a new member of the TNF family that induces apoptosis // Immunity. - 1995. - 3. - P. 673-82.Yanagisawa J., Takahashi M., Kanki H. The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis // J Biol Chem. - 1997. - 272(13). - P. 8539-45.Yin X.M. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways // Cell Res. - 2000. - 10(3). - P. 161-7.Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor // J Exp Med. - 1989. - 169(5). - P. 1747-56.