Endothelial-specific Enhancer as a Cis Element of PLAUR Regulation by TNF-alpha, IL-1beta, and VEGF


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:The expression of human PLAUR gene, which encodes the urokinase plasminogen activator receptor (uPAR), is cell- and process-specific and elevated in inflammation, cancer and senescence. Its tight regulation is achieved by regulatory elements in the gene locus, such as the promoter and several enhancers. The promoter activity is not specific to a particular cell type and has been described earlier. The proximal enhancer is endothelial-specific and responsible for the PLAUR expression pattern in endothelial cells. In this study we described the enhancer activity and its cis-regulatory elements based on the published data. We showed a possible connection of the enhancer activity with known cellular phenotypes.

作者简介

Dmitry Penkov

Laboratory of Angiogenesis, Institute of Experimental Cardiology Named after Academician V.N. Smirnov, Federal State Budgetary Institution National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation

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Email: info@benthamscience.net

Irina Beloglazova

Laboratory of Angiogenesis, Institute of Experimental Cardiology Named after Academician V.N. Smirnov, Federal State Budgetary Institution National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation

Email: info@benthamscience.net

Yelena Parfyonova

Laboratory of Angiogenesis, Institute of Experimental Cardiology Named after Academician V.N. Smirnov, Federal State Budgetary Institution National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation

Email: info@benthamscience.net

参考

  1. Stoppelli MP, Corti A, Soffientini A, Cassani G, Blasi F, Assoian RK. Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes. Proc Natl Acad Sci 1985; 82(15): 4939-43. doi: 10.1073/pnas.82.15.4939 PMID: 2991901
  2. Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol 1985; 100(1): 86-92. doi: 10.1083/jcb.100.1.86 PMID: 3880760
  3. Mondino A, Blasi F. uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 2004; 25(8): 450-5. doi: 10.1016/j.it.2004.06.004 PMID: 15275645
  4. Ismail AA, Shaker BT, Bajou K. The plasminogen–activator plasmin system in physiological and pathophysiological angiogenesis. Int J Mol Sci 2021; 23(1): 337. doi: 10.3390/ijms23010337 PMID: 35008762
  5. Ellis V, Wun TC, Behrendt N, Rønne E, Danø K. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. J Biol Chem 1990; 265(17): 9904-8. doi: 10.1016/S0021-9258(19)38757-5 PMID: 2161846
  6. Blasi F. uPA, uPAR, PAI-I: Key intersection of proteolytic, adhesive and chemotacfic highways? Immunol Today 1997; 18(9): 415-7. doi: 10.1016/S0167-5699(97)01121-3 PMID: 9293155
  7. Cubellis MV, Wun TC, Blasi F. Receptor-mediated internalization and degradation of urokinase is caused by its specific inhibitor PAI-1. EMBO J 1990; 9(4): 1079-85. doi: 10.1002/j.1460-2075.1990.tb08213.x PMID: 2157592
  8. Herz J, Clouthier DE, Hammer RE. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell 1992; 71(3): 411-21. doi: 10.1016/0092-8674(92)90511-A PMID: 1423604
  9. Nykjar A, Conese M, Christensen EI, et al. Recycling of the urokinase receptor upon internalization of the uPA:serpin complexes. EMBO J 1997; 16(10): 2610-20. doi: 10.1093/emboj/16.10.2610 PMID: 9184208
  10. Kanse SM, Kost C, Wilhelm OG, Andreasen PA, Preissner KT. The urokinase receptor is a major vitronectin-binding protein on endothelial cells. Exp Cell Res 1996; 224(2): 344-53. doi: 10.1006/excr.1996.0144 PMID: 8612711
  11. Madsen CD, Sidenius N. The interaction between urokinase receptor and vitronectin in cell adhesion and signalling. Eur J Cell Biol 2008; 87(8-9): 617-29. doi: 10.1016/j.ejcb.2008.02.003 PMID: 18353489
  12. Wei Y, Lukashev M, Simon DI, et al. Regulation of integrin function by the urokinase receptor. Science 1996; 273(5281): 1551-5. doi: 10.1126/science.273.5281.1551 PMID: 8703217
  13. Yu S, Sui Y, Wang J, et al. Crystal structure and cellular functions of uPAR dimer. Nat Commun 2022; 13(1): 1665. doi: 10.1038/s41467-022-29344-y PMID: 35351875
  14. D’Alessio S, Blasi F. The urokinase receptor as an entertainer of signal transduction. Front Biosci 2009; Volume(14): 4575-87. doi: 10.2741/3550 PMID: 19273372
  15. Madunić J. The urokinase plasminogen activator system in human cancers: An overview of its prognostic and predictive role. Thromb Haemost 2018; 118(12): 2020-36. doi: 10.1055/s-0038-1675399 PMID: 30419600
  16. Dass K, Ahmad A, Azmi AS, Sarkar SH, Sarkar FH. Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 2008; 34(2): 122-36. doi: 10.1016/j.ctrv.2007.10.005 PMID: 18162327
  17. Alfano D, Franco P, Stoppelli MP. Modulation of cellular function by the urokinase receptor signalling: A mechanistic view. Front Cell Dev Biol 2022; 10: 818616. doi: 10.3389/fcell.2022.818616 PMID: 35493073
  18. Metrangolo V, Ploug M, Engelholm LH. The Urokinase Receptor (uPAR) as a "Trojan Horse" in targeted cancer therapy: Challenges and opportunities. Cancers 2021; 13(21): 5376.
  19. Lv T, Zhao Y, Jiang X, et al. uPAR: An essential factor for tumor development. J Cancer 2021; 12(23): 7026-40. doi: 10.7150/jca.62281 PMID: 34729105
  20. Li Santi A, Napolitano F, Montuori N, Ragno P. The urokinase receptor: A multifunctional receptor in cancer cell biology. Therapeutic implications. Int J Mol Sci 2021; 22(8): 4111. doi: 10.3390/ijms22084111 PMID: 33923400
  21. Rømer J, Lund LR, Eriksen J, Pyke C, Kristensen P, Danø K. The receptor for urokinase-type plasminogen activator is expressed by keratinocytes at the leading edge during re-epithelialization of mouse skin wounds. J Invest Dermatol 1994; 102(4): 519-22. doi: 10.1111/1523-1747.ep12373187 PMID: 8151132
  22. del Toro R, Prahst C, Mathivet T, et al. Identification and functional analysis of endothelial tip cell–enriched genes. Blood 2010; 116(19): 4025-33. doi: 10.1182/blood-2010-02-270819 PMID: 20705756
  23. Brunner PM, Heier PC, Mihaly-Bison J, Priglinger U, Binder BR, Prager GW. Density enhanced phosphatase-1 down-regulates urokinase receptor surface expression in confluent endothelial cells. Blood 2011; 117(15): 4154-61. doi: 10.1182/blood-2010-09-307694 PMID: 21304107
  24. Rubina KA, Sysoeva VY, Zagorujko EI, et al. Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell carcinomas. Arch Dermatol Res 2017; 309(6): 433-42. doi: 10.1007/s00403-017-1738-z PMID: 28429105
  25. Kanno Y. The uPA/uPAR system orchestrates the inflammatory response, vascular homeostasis, and immune system in fibrosis progression. Int J Mol Sci 2023; 24(2): 1796. doi: 10.3390/ijms24021796 PMID: 36675310
  26. Amor C, Feucht J, Leibold J, et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 2020; 583(7814): 127-32. doi: 10.1038/s41586-020-2403-9 PMID: 32555459
  27. Li JH, Chen YY. A fresh approach to targeting aging cells: CAR-T cells enhance senolytic specificity. Cell Stem Cell 2020; 27(2): 192-4. doi: 10.1016/j.stem.2020.07.010 PMID: 32763179
  28. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473(7347): 298-307. doi: 10.1038/nature10144 PMID: 21593862
  29. Luttun A, Carmeliet P. De novo vasculogenesis in the heart. Cardiovasc Res 2003; 58(2): 378-89. doi: 10.1016/S0008-6363(03)00258-X PMID: 12757872
  30. Lijnen HR. Elements of the fibrinolytic system. Ann N Y Acad Sci 2001; 936(1): 226-36. doi: 10.1111/j.1749-6632.2001.tb03511.x PMID: 11460480
  31. Liu G, Chen T, Ding Z, Wang Y, Wei Y, Wei X. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment. Cell Prolif 2021; 54(4): e13009. doi: 10.1111/cpr.13009 PMID: 33655556
  32. Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: Beyond discovery and development. Cell 2019; 176(6): 1248-64. doi: 10.1016/j.cell.2019.01.021 PMID: 30849371
  33. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9(6): 669-76. doi: 10.1038/nm0603-669 PMID: 12778165
  34. Melincovici CS, Bo AB, Mihu C, Istrate M. Vascular endothelial growth factor (VEGF) – Key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018; 59(2): 455-67.
  35. Prager GW, Breuss JM, Steurer S, Mihaly J, Binder BR. Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells. Blood 2004; 103(3): 955-62. doi: 10.1182/blood-2003-07-2214 PMID: 14525763
  36. Blasi F, Carmeliet P. uPAR: A versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3(12): 932-43. doi: 10.1038/nrm977 PMID: 12461559
  37. Zhao R, Le K, Moghadasian MH, Shen GX. Reduced monocyte adhesion to aortae of diabetic plasminogen activator inhibitor-1 knockout mice. Inflamm Res 2017; 66(9): 783-92. doi: 10.1007/s00011-017-1057-z PMID: 28550522
  38. Raghu H, Lakka SS, Gondi CS, et al. Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines. PLoS One 2010; 5(8): e12458. doi: 10.1371/journal.pone.0012458 PMID: 20805979
  39. Alexander RA, Prager GW, Mihaly-Bison J, et al. VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution. Cardiovasc Res 2012; 94(1): 125-35. doi: 10.1093/cvr/cvs017 PMID: 22287577
  40. Unseld M, Chilla A, Pausz C, et al. PTEN expression in endothelial cells is down-regulated by uPAR to promote angiogenesis. Thromb Haemost 2015; 114(8): 379-89. doi: 10.1160/TH15-01-0016 PMID: 25925849
  41. Trisciuoglio D, Iervolino A, Candiloro A, et al. bcl-2 induction of urokinase plasminogen activator receptor expression in human cancer cells through Sp1 activation: Involvement of ERK1/ERK2 activity. J Biol Chem 2004; 279(8): 6737-45. doi: 10.1074/jbc.M308938200 PMID: 14660675
  42. Margheri F, Chillà A, Laurenzana A, et al. Endothelial progenitor cell–dependent angiogenesis requires localization of the full-length form of uPAR in caveolae. Blood 2011; 118(13): 3743-55. doi: 10.1182/blood-2011-02-338681 PMID: 21803847
  43. Herkenne S, Paques C, Nivelles O, et al. The interaction of uPAR with VEGFR2 promotes VEGF-induced angiogenesis. Sci Signal 2015; 8(403): ra117-7. doi: 10.1126/scisignal.aaa2403 PMID: 26577922
  44. Mahabeleshwar GH, Feng W, Reddy K, Plow EF, Byzova TV. Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis. Circ Res 2007; 101(6): 570-80. doi: 10.1161/CIRCRESAHA.107.155655 PMID: 17641225
  45. Dewerchin M, Nuffelen AV, Wallays G, et al. Generation and characterization of urokinase receptor-deficient mice. J Clin Invest 1996; 97(3): 870-8. doi: 10.1172/JCI118489 PMID: 8609247
  46. Dergilev KV, Beloglazova IB, Tsokolaeva ZI, Vasilets YD, Parfenova EV. Deficiency of urokinase-type plasminogen activator receptor is associated with the development of perivascular fibrosis in mouse heart. Bull Exp Biol Med 2022; 173(1): 5-9. doi: 10.1007/s10517-022-05480-9 PMID: 35622258
  47. Manetti M, Rosa I, Fazi M, et al. Systemic sclerosis-like histopathological features in the myocardium of uPAR-deficient mice. Ann Rheum Dis 2016; 75(2): 474-8. doi: 10.1136/annrheumdis-2015-207803 PMID: 26269399
  48. Balsara RD, Merryman R, Virjee F, Northway C, Castellino FJ, Ploplis VA. A deficiency of uPAR alters endothelial angiogenic function and cell morphology. Vasc Cell 2011; 3(1): 10. doi: 10.1186/2045-824X-3-10 PMID: 21535874
  49. Casey JR, Petranka JG, Kottra J, Fleenor DE, Rosse WF. The structure of the urokinase-type plasminogen activator receptor gene. Blood 1994; 84(4): 1151-6. doi: 10.1182/blood.V84.4.1151.1151 PMID: 8049431
  50. Pyke C, Eriksen J, Solberg H, et al. An alternatively spliced variant of mRNA for the human receptor for urokinase plasminogen activator. FEBS Lett 1993; 326(1-3): 69-74. doi: 10.1016/0014-5793(93)81763-P PMID: 8392005
  51. Choong PFM, Nadesapillai APW. Urokinase plasminogen activator system: A multifunctional role in tumor progression and metastasis. Clin Orthop Relat Res 2003; 415(415): S46-58. doi: 10.1097/01.blo0000093845.72468.bd PMID: 14600592
  52. Wang H, Yan C, Asangani I, Allgayer H, Boyd DD. Identification of an histone H3 acetylated/K4-methylated-bound intragenic enhancer regulatory for urokinase receptor expression. Oncogene 2007; 26(14): 2058-70. doi: 10.1038/sj.onc.1210003 PMID: 17001307
  53. Wang H, Yang L, Jamaluddin MS, Boyd DD. The Kruppel-like KLF4 transcription factor, a novel regulator of urokinase receptor expression, drives synthesis of this binding site in colonic crypt luminal surface epithelial cells. J Biol Chem 2004; 279(21): 22674-83. doi: 10.1074/jbc.M401257200 PMID: 15031282
  54. Li C, Xu Q. Mechanical stress-initiated signal transductions in vascular smooth muscle cells. Cell Signal 2000; 12(7): 435-45. doi: 10.1016/S0898-6568(00)00096-6 PMID: 10989277
  55. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer 2013; 13(12): 871-82. doi: 10.1038/nrc3627 PMID: 24263190
  56. Wang Y, Jones CJ, Dang J, Liang X, Olsen JE, Doe WF. Human urokinase receptor expression is inhibited by amiloride and induced by tumor necrosis factor and phorbol ester in colon cancer cells. FEBS Lett 1994; 353(2): 138-42. doi: 10.1016/0014-5793(94)01032-3 PMID: 7926038
  57. Nykjaer A, Møller B, Todd RF III, et al. Urokinase receptor. An activation antigen in human T lymphocytes. J Immunol 1994; 152(2): 505-16. doi: 10.4049/jimmunol.152.2.505 PMID: 8283034
  58. Plesner T, Ploug M, Ellis V, et al. The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils. Blood 1994; 83(3): 808-15. doi: 10.1182/blood.V83.3.808.808 PMID: 8298141
  59. Langer DJ, Kuo A, Kariko K, et al. Regulation of the endothelial cell urokinase-type plasminogen activator receptor. Evidence for cyclic AMP-dependent and protein kinase C-dependent pathways. Circ Res 1993; 72(2): 330-40. doi: 10.1161/01.RES.72.2.330 PMID: 7678205
  60. Dang J, Wang Y, Doe WF. Sodium butyrate inhibits expression of urokinase and its receptor mRNAs at both transcription and post-transcription levels in colon cancer cells. FEBS Lett 1995; 359(2-3): 147-50. doi: 10.1016/0014-5793(95)00029-9 PMID: 7867787
  61. Lund LR, Rønne E, Roldan AL, et al. Urokinase receptor mRNA level and gene transcription are strongly and rapidly increased by phorbol myristate acetate in human monocyte-like U937 cells. J Biol Chem 1991; 266(8): 5177-81. doi: 10.1016/S0021-9258(19)67771-9 PMID: 1848242
  62. Sitrin RG, Todd RF III, Mizukami IF, Gross TJ, Shollenberger SB, Gyetko MR. Cytokine-specific regulation of urokinase receptor (CD87) expression by U937 mononuclear phagocytes. Blood 1994; 84(4): 1268-75. PMID: 8049441
  63. Kirchheimer JC, Nong YH, Remold HG. IFN-gamma, tumor necrosis factor-alpha, and urokinase regulate the expression of urokinase receptors on human monocytes. J Immunol 1988; 141(12): 4229-34. doi: 10.4049/jimmunol.141.12.4229 PMID: 2848891
  64. Büchler P, Reber HA, Tomlinson JS, et al. Transcriptional regulation of urokinase-type plasminogen activator receptor by hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver cancer. Neoplasia 2009; 11(2): 196-IN12. doi: 10.1593/neo.08734 PMID: 19177204
  65. Wang Y. The role and regulation of urokinase-type plasminogen activator receptor gene expression in cancer invasion and metastasis. Med Res Rev 2001; 21(2): 146-70. doi: 10.1002/1098-1128(200103)21:23.0.CO;2-B PMID: 11223863
  66. Soravia E, Grebe A, De Luca P, et al. A conserved TATA-less proximal promoter drives basal transcription from the urokinase- type plasminogen activator receptor gene. Blood 1995; 86(2): 624-35. doi: 10.1182/blood.V86.2.624.bloodjournal862624 PMID: 7605992
  67. Haun RS, Moss J, Vaughan M. Characterization of the human ADP-ribosylation factor 3 promoter. Transcriptional regulation of a TATA-less promoter. J Biol Chem 1993; 268(12): 8793-800. doi: 10.1016/S0021-9258(18)52944-6 PMID: 8473323
  68. Chen X, Xu Y. Structural insights into assembly of transcription preinitiation complex. Curr Opin Struct Biol 2022; 75: 102404. doi: 10.1016/j.sbi.2022.102404 PMID: 35700575
  69. Kaczynski J, Cook T, Urrutia R. Sp1- and Krüppel-like transcription factors. Genome Biol 2003; 4(2): 206. doi: 10.1186/gb-2003-4-2-206 PMID: 12620113
  70. (a) Lee CM, Barber GP, Casper J, et al. UCSC genome browser enters 20th year. Nucleic Acids Res 2019; 48(D1): gkz1012. doi: 10.1093/nar/gkz1012 PMID: 31691824; (b) Raney BJ, Barber GP, Pagès BA, et al. The UCSC genome browser database: 2024 update. Nucleic Acids Res 2023; 52: D1082-8. doi: 10.1093/nar/gkad987 PMID: 37953330; (c) Brown JD, Lin CY, Duan Q, et al. NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 2014; 56(2): 219-31. doi: 10.1016/j.molcel.2014.08.024 PMID: 25263595
  71. Linnemann AK, O’Geen H, Keles S, Farnham PJ, Bresnick EH. Genetic framework for GATA factor function in vascular biology. Proc Natl Acad Sci 2011; 108(33): 13641-6. doi: 10.1073/pnas.1108440108 PMID: 21808000
  72. Masquilier D, Corsi SP. Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. J Biol Chem 1992; 267(31): 22460-6. doi: 10.1016/S0021-9258(18)41694-8 PMID: 1429597
  73. Kawasaki K, Fukaya T. Regulatory landscape of enhancer-mediated transcriptional activation. Trends Cell Biol 2024; 13: S0962-8924(24)00020-5. doi: 10.1016/j.tcb.2024.01.008 PMID: 38355349
  74. Karpinska MA, Oudelaar AM. The role of loop extrusion in enhancer-mediated gene activation. Curr Opin Genet Dev 2023; 79: 102022. doi: 10.1016/j.gde.2023.102022 PMID: 36842325
  75. Weintraub AS, Li CH, Zamudio AV, et al. YY1 is a structural regulator of enhancer-promoter loops. Cell 2017; 171(7): 1573-1588.e28. doi: 10.1016/j.cell.2017.11.008 PMID: 29224777
  76. Zuin J, Roth G, Zhan Y, et al. Nonlinear control of transcription through enhancer–promoter interactions. Nature 2022; 604(7906): 571-7. doi: 10.1038/s41586-022-04570-y PMID: 35418676
  77. Zhang S, Übelmesser N, Barbieri M, Papantonis A. Enhancer–promoter contact formation requires RNAPII and antagonizes loop extrusion. Nat Genet 2023; 55(5): 832-40. doi: 10.1038/s41588-023-01364-4 PMID: 37012454
  78. Kubo N, Ishii H, Xiong X, et al. Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation. Nat Struct Mol Biol 2021; 28(2): 152-61. doi: 10.1038/s41594-020-00539-5 PMID: 33398174
  79. (a) Pope BD, Ryba T, Dileep V, et al. Topologically associating domains are stable units of replication-timing regulation. Nature 2014; 515(7527): 402-5. doi: 10.1038/nature13986 PMID: 25409831; (b) Zhang B, Day DS, Ho JW, et al. A dynamic H3K27ac signature identifies VEGFA-stimulated endothelial enhancers and requires EP300 activity. Genome Res 2013; 23(6): 917-27. doi: 10.1101/gr.149674.112 PMID: 23547170
  80. Ghouili F, Roumaud P, Martin LJ. Gja1 expression is regulated by cooperation between SOX8/SOX9 and cJUN transcription factors in TM4 and 15P-1 Sertoli cell lines. Mol Reprod Dev 2018; 85(11): 875-86. doi: 10.1002/mrd.23049 PMID: 30080944
  81. Hogan NT, Whalen MB, Stolze LK, et al. Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells. eLife 2017; 6: e22536. doi: 10.7554/eLife.22536 PMID: 28585919
  82. Karin M, Lin A. NF-κB at the crossroads of life and death. Nat Immunol 2002; 3(3): 221-7. doi: 10.1038/ni0302-221 PMID: 11875461
  83. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001; 11(9): 372-7. doi: 10.1016/S0962-8924(01)02064-5 PMID: 11514191
  84. Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 2009; 27(1): 693-733. doi: 10.1146/annurev.immunol.021908.132641 PMID: 19302050
  85. Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 2009; 1(5): a000141. doi: 10.1101/cshperspect.a000141 PMID: 20066113
  86. Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA. Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms. Int Rev Cytol 2006; 252: 129-61. doi: 10.1016/S0074-7696(06)52002-9 PMID: 16984817

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