Genomes and Genes
Summary: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
- Wang T, Leventis R, Silvius J. Artificially lipid-anchored proteins can elicit clustering-induced intracellular signaling events in Jurkat T-lymphocytes independent of lipid raft association. J Biol Chem. 2005;280:22839-46 pubmed
- Rushmere N, Knowlden J, Gee J, Harper M, Robertson J, Morgan B, et al. Analysis of the level of mRNA expression of the membrane regulators of complement, CD59, CD55 and CD46, in breast cancer. Int J Cancer. 2004;108:930-6 pubmed..These data provide new information on expression of these important regulators in breast cancer and suggest that CD46 should be evaluated as a novel prognostic indicator. ..
- Baalasubramanian S, Harris C, Donev R, Mizuno M, Omidvar N, Song W, et al. CD59a is the primary regulator of membrane attack complex assembly in the mouse. J Immunol. 2004;173:3684-92 pubmed..Erythrocyte CD59b did not inhibit complement lysis except when CD59a was absent or blocked. These data confirm that CD59a is the primary regulator of complement membrane attack in mouse. ..
- Turnberg D, Botto M, Warren J, Morgan B, Walport M, Cook H. CD59a deficiency exacerbates accelerated nephrotoxic nephritis in mice. J Am Soc Nephrol. 2003;14:2271-9 pubmed..The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex-mediated glomerulonephritis. ..
- Qin X, Goldfine A, Krumrei N, Grubissich L, Acosta J, Chorev M, et al. Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes. Diabetes. 2004;53:2653-61 pubmed..We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes. ..
- De Nardo C, Fonsatti E, Sigalotti L, Calabro L, Colizzi F, Cortini E, et al. Recombinant transmembrane CD59 (CD59-TM) confers complement resistance to GPI-anchored protein defective melanoma cells. J Cell Physiol. 2002;190:200-6 pubmed..Further unveiling of the molecular mechanism that turns off CD59 expression in human melanoma cells will help to set-up more effective therapeutic strategies utilizing C-activating mAb in melanoma patients. ..
- van Beek J, van Meurs M, t Hart B, Brok H, Neal J, Chatagner A, et al. Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation. J Immunol. 2005;174:2353-65 pubmed..We conclude that increased CD55 expression by neurons may represent a key protective signaling mechanism mobilized by brain cells to withstand complement activation and to survive within an inflammatory site. ..
- Echeverri K, Tanaka E. Proximodistal patterning during limb regeneration. Dev Biol. 2005;279:391-401 pubmed
- Qin X, Dobarro M, Bedford S, Ferris S, Miranda P, Song W, et al. Further characterization of reproductive abnormalities in mCd59b knockout mice: a potential new function of mCd59 in male reproduction. J Immunol. 2005;175:6294-302 pubmed
- An G, Miwa T, Song W, Lawson J, Rader D, Zhang Y, et al. CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice. Mol Immunol. 2009;46:1702-9 pubmed publisher..The protective role of CD59 was gender-biased and most likely involved prevention of MAC-mediated vascular injury, with possible contribution from an undefined effect on plasma cholesterol homeostasis. ..
- Giddings K, Zhao J, Sims P, Tweten R. Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin. Nat Struct Mol Biol. 2004;11:1173-8 pubmed..ILY specifically binds to huCD59 via residues that are the binding site for the C8alpha and C9 complement proteins. These studies provide a new model for the mechanism of cellular recognition by a CDC. ..
- Williams A, Mizuno M, Richards P, Holt D, Morgan B. Deletion of the gene encoding CD59a in mice increases disease severity in a murine model of rheumatoid arthritis. Arthritis Rheum. 2004;50:3035-44 pubmed
- Longhi M, Harris C, Morgan B, Gallimore A. Holding T cells in check--a new role for complement regulators?. Trends Immunol. 2006;27:102-8 pubmed..Here we review these studies, which reveal another important link between the innate and the adaptive immune system. ..
- Longhi M, Williams A, Wise M, Morgan B, Gallimore A. CD59a deficiency exacerbates influenza-induced lung inflammation through complement-dependent and -independent mechanisms. Eur J Immunol. 2007;37:1266-74 pubmed..These results demonstrate that CD59a, previously defined as a complement regulator, modulates both the innate and adaptive immune response to influenza virus by both complement-dependent and -independent mechanisms. ..
- Pedersen E, Aass H, Rootwelt T, Fung M, Lambris J, Mollnes T. CD59 efficiently protects human NT2-N neurons against complement-mediated damage. Scand J Immunol. 2007;66:345-51 pubmed..In conclusion, CD59 is essential for protecting human NT2-N neurons against complement-mediated damage, which is known to occur in a number of clinical conditions including stroke. ..
- Wu G, Hu W, Shahsafaei A, Song W, Dobarro M, Sukhova G, et al. Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex. Circ Res. 2009;104:550-8 pubmed publisher..These combined results highlight the atherogenic role of MAC and the atheroprotective role of CD59 and suggest that inhibition of MAC formation may provide a therapeutic approach for the treatment of atherosclerosis. ..
- Kolev M, Tediose T, Sivasankar B, Harris C, Thome J, Morgan B, et al. Upregulating CD59: a new strategy for protection of neurons from complement-mediated degeneration. Pharmacogenomics J. 2010;10:12-9 pubmed publisher..This study brings new insight into immunopharmacological research that may serve to inhibit neuronal death triggered by the terminal pathway of complement activation. ..
- Turnberg D, Botto M, Lewis M, Zhou W, Sacks S, Morgan B, et al. CD59a deficiency exacerbates ischemia-reperfusion injury in mice. Am J Pathol. 2004;165:825-32 pubmed
- Fraser D, Harris C, Williams A, Mizuno M, Gallagher S, Smith R, et al. Generation of a recombinant, membrane-targeted form of the complement regulator CD59: activity in vitro and in vivo. J Biol Chem. 2003;278:48921-7 pubmed..This novel type of agent, termed sCD59-APT542, offers for the first time the prospect of efficient and specific inhibition of membrane attack complex activity in vivo. ..
- Harris C, Hanna S, Mizuno M, Holt D, Marchbank K, Morgan B. Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison. Immunology. 2003;109:117-26 pubmed..These findings demonstrate that the broadly distributed mCD59a is the key regulator of the terminal complement pathway in mice whereas CD59b, expressed only in testis and on sperm, probably plays other roles in vivo. ..
- da Silva S, Gates P, Brockes J. The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration. Dev Cell. 2002;3:547-55 pubmed..Prod 1 is therefore a cell surface protein implicated in the local cell-cell interactions mediating positional identity...
- Yamada K, Miwa T, Liu J, Nangaku M, Song W. Critical protection from renal ischemia reperfusion injury by CD55 and CD59. J Immunol. 2004;172:3869-75 pubmed..Our findings suggest a rationale for anti-complement therapies aimed at preventing microvascular injury during ischemia reperfusion, and the CD55(-/-)CD59(-/-) mouse provides a useful animal model in this regard. ..
- Soltani C, Hotze E, Johnson A, Tweten R. Specific protein-membrane contacts are required for prepore and pore assembly by a cholesterol-dependent cytolysin. J Biol Chem. 2007;282:15709-16 pubmed..These studies reveal that pore formation by ILY, and probably other CDCs, is affected by an intricate and coupled sequence of interactions between domain 4 and the membrane. ..
- Yan J, Allendorf D, Li B, Yan R, Hansen R, Donev R. The role of membrane complement regulatory proteins in cancer immunotherapy. Adv Exp Med Biol. 2008;632:159-74 pubmed..Strategies have been developed to address these issues and more in vivo studies are needed to further validate these combination approaches. ..
- Stahel P, Flierl M, Morgan B, Persigehl I, Stoll C, Conrad C, et al. Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J Neuroinflammation. 2009;6:2 pubmed publisher..The exact mechanisms of complement MAC-induced secondary neuronal cell death after head injury require further investigation. ..
- Brockes J, Kumar A. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science. 2005;310:1919-23 pubmed..The blastema can regenerate autonomously as a self-organizing system over variable linear dimensions. Here we consider the prospects for limb regeneration in mammals from this viewpoint. ..
- Suzuki K, Fujiwara T, Edidin M, Kusumi A. Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. J Cell Biol. 2007;177:731-42 pubmed
- Kimberley F, Sivasankar B, Paul Morgan B. Alternative roles for CD59. Mol Immunol. 2007;44:73-81 pubmed..In this review, we examine the progression of research in this area and explore the alternative functions of CD59 that have recently been defined. ..
- Huang Y, Smith C, Song H, Morgan B, Abagyan R, Tomlinson S. Insights into the human CD59 complement binding interface toward engineering new therapeutics. J Biol Chem. 2005;280:34073-9 pubmed..Based on the enhanced activity of membrane-bound mutant CD59 molecules, clinically relevant soluble mutant CD59-based proteins were prepared and shown to have up to a 3-fold increase in complement inhibitory activity. ..
- Ramaglia V, King R, Morgan B, Baas F. Deficiency of the complement regulator CD59a exacerbates Wallerian degeneration. Mol Immunol. 2009;46:1892-6 pubmed publisher..The number of endoneurial macrophages was significantly higher in CD59a deficient mice compared to wildtypes at 1 day post-injury. These findings are relevant to the understanding of the mechanisms of axon loss in injury and disease...
- Mitchell J, Kanca O, McIntyre B. Lipid microdomain clustering induces a redistribution of antigen recognition and adhesion molecules on human T lymphocytes. J Immunol. 2002;168:2737-44 pubmed
- Mead R, Neal J, Griffiths M, Linington C, Botto M, Lassmann H, et al. Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis. Lab Invest. 2004;84:21-8 pubmed..These findings are relevant to some types of human demyelination, where abundant deposits of MAC are found in association with pathology. ..
- Kumar A, Godwin J, Gates P, Garza Garcia A, Brockes J. Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science. 2007;318:772-7 pubmed..Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration...
- Gorter A, Meri S. Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today. 1999;20:576-82 pubmed..Here, Arko Gorter and Seppo Meri discuss the implications of complement resistance for the immunotherapeutic treatment of solid tumors with monoclonal antibodies. ..
- Mason J, Yarwood H, Sugars K, Morgan B, Davies K, Haskard D. Induction of decay-accelerating factor by cytokines or the membrane-attack complex protects vascular endothelial cells against complement deposition. Blood. 1999;94:1673-82 pubmed
- Qian Y, Qin X, Miwa T, Sun X, Halperin J, Song W. Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59. J Immunol. 2000;165:2528-34 pubmed..These results revealed the existence of two distinct cd59 genes in the mouse that are differentially regulated and that may have nonoverlapping physiological functions in vivo. ..
- Bodian D, Davis S, Morgan B, Rushmere N. Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59. J Exp Med. 1997;185:507-16 pubmed..Additional experiments showed that the expression and function of CD59 are both glycosylation independent. ..
- Yamashina M, Ueda E, Kinoshita T, Takami T, Ojima A, Ono H, et al. Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1990;323:1184-9 pubmed
- Rooney I, Morgan B. Characterization of the membrane attack complex inhibitory protein CD59 antigen on human amniotic cells and in amniotic fluid. Immunology. 1992;76:541-7 pubmed..These data suggest that HAEC secrete into AF a form of CD59 Ag which retains inhibitory activity and which may be important in protection of the foetus from maternal complement in utero. ..
- Ninomiya H, Sims P. The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9. J Biol Chem. 1992;267:13675-80 pubmed..Partial reduction of C8 alpha-gamma revealed that only C8 alpha polypeptide exhibited affinity for CD59, and no specific binding to the C8 gamma chain was detected.(ABSTRACT TRUNCATED AT 400 WORDS) ..
- Davies A, Simmons D, Hale G, Harrison R, Tighe H, Lachmann P, et al. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med. 1989;170:637-54 pubmed
- Kieffer B, Driscoll P, Campbell I, Willis A, van der Merwe P, Davis S. Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins. Biochemistry. 1994;33:4471-82 pubmed..The topology of sCD59 is similar to that of the snake venom neurotoxins and consistent with an evolutionary relationship existing between the Ly6SF and the neurotoxins. ..
- Fletcher C, Harrison R, Lachmann P, Neuhaus D. Structure of a soluble, glycosylated form of the human complement regulatory protein CD59. Structure. 1994;2:185-99 pubmed..We have used the structure, in combination with existing biochemical data, to identify residues that may be involved in C8 binding. ..
- Solomon K, Rudd C, Finberg R. The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes. Proc Natl Acad Sci U S A. 1996;93:6053-8 pubmed..These experiments suggest a potential role of G proteins in the transduction of signals generated by GPI-anchored molecules expressed on lymphocytes of both mouse and human. ..
- Powell M, Marchbank K, Rushmere N, van den Berg C, Morgan B. Molecular cloning, chromosomal localization, expression, and functional characterization of the mouse analogue of human CD59. J Immunol. 1997;158:1692-702 pubmed..Western blot analysis revealed that both expressed and endogenous mCD59 had a molecular mass of 22 to 24 kDa. ..
- Stulnig T, Berger M, Sigmund T, Stockinger H, Horejsi V, Waldhausl W. Signal transduction via glycosyl phosphatidylinositol-anchored proteins in T cells is inhibited by lowering cellular cholesterol. J Biol Chem. 1997;272:19242-7 pubmed..These results suggest that cellular cholesterol is an important prerequisite for signal transduction via GPI-anchored proteins beyond formation of membrane domains. ..
- Holt D, Botto M, Bygrave A, Hanna S, Walport M, Morgan B. Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria. Blood. 2001;98:442-9 pubmed..CD59(-/-) mice will provide a tool for characterizing the importance of CD59 in protection of self tissues from membrane attack complex damage in health and during diseases in which complement is activated...
- Qin X, Miwa T, Aktas H, Gao M, Lee C, Qian Y, et al. Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b. Mamm Genome. 2001;12:582-9 pubmed..These results suggest that even though Cd59a and Cd59b are expressed in multiple tissues, they may play some different roles, particularly in reproduction. ..
- Hahn W, Menu E, Bothwell A, Sims P, Bierer B. Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science. 1992;256:1805-7 pubmed..These observations suggest that direct interactions between CD2 and both CD58 and CD59 contribute to T cell activation and adhesion. ..