Sjogren sindrom antigen B
Sjogren sindrom antigen B (akronim SSB — Sjögren syndrome type B antigen), takođe poznat i kao lupusni autoantigen (La) ili SSB/La, je antigen najčešće povezana sa nastankom autoimunskih poremećaja, kao što Sjogrenov sindrom i sistemski eritemski lupus.[4][5] SSB/La po svom sastavu je protein koji je evoluirao od kvasca do čoveka. Obično se nalazi u ćelijskom jezgru i citoplazmi, gde igra fundamentalnu ulogu u različitim procesima metabolizma RNK.[6]
Uloga
urediSSB/La je, prema istraživanjima, uključen u različite procese metabolizma RNK, uključujući tu i njegovo posredovanje u procesu nastajanja transkripata RNK polimeraze III i prekursora tRNAs (pre-tRNAs), kroz prihvatanje za karakteristične 3′ UUU (OH) završetke.
Ulaskom u metaboličke procese SSB/La štiti pre-tRNAs od nespecifične egzonukleaze i digestijom obezbeđuje pravilnu transformaciju lidera 5' i 3' sekvenci pre-tRNAs u specifične ribonukleozome kao što su RNase P i RNase Z.[7][8][9]
Reaktivnost SSB/La protein je prvobitno bila otkrivena u autoantitelima bolesnika sa Sjogrenovim sindrom i sistemskim eritemskim lupusom. Studije u tim bolestima pokazale su da miRNA imaju važnu ulogu u održavanju homeostaze imunskog sistema tj u očuvanju autoimunosti.[10]
Bolesnici koji pate od Sjogrenovog sindroma i sistemskog eritemskog lupusa, često proizvode autoantitela protiv specifičnih klasa RNK za vezivanja proteina. Ovi autoantigeni (pored mnogih drugih) uključuju i SSB/La autantitela.[11][12]
Otkriće da autoantigen SSB/La funkcioniše kao ključni regulator globalne ekspresije miRNA, nametnuolo je potrebu za novim istraživanjima kako bi se utvrdilo da li inaktivacijom SSB/La autoantitela, može izostati regulacija ekspresije gena, i/ili fosforilacija, koja direktno doprinosi patogenezi autoimunskih bolesti.[13][14]
Interakcija
urediU brojnim studijama dokazano je da Sjogren sindrom antigen B stupa u interakciju sa nukleolinom.[15]
Značaj SSB/La u dijagnostici
urediTestovima krvi može se utvrditi da li bolesnik ima visok nivo antitela koja ukazuju na određena autoimunske bolesti, kao što su to anti-nuklearna antitela (ANA) i reumatoidni faktor (SS/Ro), koji su povezani sa autoimunskim bolestima.
Tako se npr. u dijagnostici Sjogrenovog sindroma i sistemskog eritemskog lupusa koristi metoda određivanja tipična anti-nuklearnog antitela (ANA ) SSB/La i SSS/Ro, od kojih je. SSB/La daleko pouzdaniji kod ovih bolesti od SSS/Ro koji je manje specifičan jer je pored u ovim bolestima prisutan i u brojnim drugim autoimunskim bolestima.[16]
Vidi još
urediIzvori
uredi- ^ a b v GRCm38: Ensembl release 89: ENSMUSG00000068882 - Ensembl, May 2017
- ^ „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mattioli M., Reichlin M. (1974) Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen. Arthritis Rheum. 17, 421–429
- ^ Bousquet-Antonelli C., Deragon J. M. (2009) A comprehensive analysis of the La-motif protein superfamily. RNA 15, 750–764
- ^ Wolin S. L., Cedervall T. (2002) The La protein. Annu. Rev. Biochem. 71, 375–403
- ^ Chakshusmathi G., Kim S. D., Rubinson D. A., Wolin S. L. (2003) A La protein requirement for efficient pre-tRNA folding. EMBO J. 22, 6562–6572
- ^ Fan H., Goodier J. L., Chamberlain J. R., Engelke D. R., Maraia R. J. (1998) 5′ processing of tRNA precursors can be modulated by the human La antigen phosphoprotein. Mol. Cell. Biol. 18, 3201–3211 Abstract/FREE Full Text
- ^ Yoo C. J., Wolin S. L. (1997) The La protein in Schizosaccharomyces pombe. A conserved yet dispensable phosphoprotein that functions in tRNA maturation. Cell 89, 393–402
- ^ Taganov K. D., Boldin M. P., Baltimore D. (2007) MicroRNAs and immunity. Tiny players in a big field. Immunity 26, 133–137
- ^ Pruijn G. J. (2006) The RNA interference pathway. A new target for autoimmunity. Arthritis Res. Ther. 8, 110
- ^ Jakymiw A., Ikeda K., Fritzler M. J., Reeves W. H., Satoh M., Chan E. K. (2006) Autoimmune targeting of key components of RNA interference. Arthritis Res. Ther. 8, R87
- ^ „Entrez Gene: SSB Sjögren's syndrome antigen B (autoantigen La)”.
- ^ Teplova, Marianna; Yuan, Yu-Ren; Phan, Anh Tuân; Malinina, Lucy; Ilin, Serge; Teplov, Alexei; Patel, Dinshaw J. (2006). „Structural Basis for Recognition and Sequestration of UUUOH 3′ Temini of Nascent RNA Polymerase III Transcripts by la, a Rheumatic Disease Autoantigen”. Molecular Cell. 21 (1): 75—85. PMC 4689297
. PMID 16387655. doi:10.1016/j.molcel.2005.10.027.
- ^ Fouraux, Michael A; Bouvet Philippe, Verkaart Sjoerd, van Venrooij Walther J, Pruijn Ger J M (2002). „Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes”. J. Mol. Biol. England. 320 (3): 475—88. ISSN 0022-2836. PMID 12096904. doi:10.1016/S0022-2836(02)00518-1.
- ^ Sjogren Syndrome Antigen B (SSB)/La Promotes Global MicroRNA Expression by Binding MicroRNA Precursors through Stem-Loop Recognition J Biol Chem 2013 288:723-736 AbstractFull Text (HTML)Full Text (PDF)
Literatura
uredi- Kohsaka, H.; K, Yamamoto; Fujii, H. (1990). „Fine epitope mapping of the human SS-B/La protein. Identification of a distinct autoepitope homologous to a viral gag polyprotein.”. J. Clin. Invest. 85 (5): 1566—74. PMC 296607 . PMID 1692037. doi:10.1172/JCI114606.
- Sturgess, AD; Peterson, MG; McNeilage, LJ (1988). „Characteristics and epitope mapping of a cloned human autoantigen La.”. J. Immunol. 140 (9): 3212—8. PMID 2452201. S2CID 1863804. doi:10.4049/jimmunol.140.9.3212.
- Rauh AJ, Hornig H, Lührmann R (1989). „At least three distinct B cell epitopes reside in the C-terminal half of La protein, as determined by a recombinant DNA approach.”. Eur. J. Immunol. 18 (12): 2049—57. PMID 2464497. S2CID 7014818. doi:10.1002/eji.1830181227.
- Chan EK, Sullivan KF, Tan EM (1989). „Ribonucleoprotein SS-B/La belongs to a protein family with consensus sequences for RNA-binding.”. Nucleic Acids Res. 17 (6): 2233—44. PMC 317593 . PMID 2468131. doi:10.1093/nar/17.6.2233.
- Gottlieb E, Steitz JA (1989). „Function of the mammalian La protein: evidence for its action in transcription termination by RNA polymerase III.”. EMBO J. 8 (3): 851—61. PMC 400884 . PMID 2470590. doi:10.1002/j.1460-2075.1989.tb03446.x.
- Chambers JC, Kenan D, Martin BJ, Keene JD (1989). „Genomic structure and amino acid sequence domains of the human La autoantigen.”. J. Biol. Chem. 263 (34): 18043—51. PMID 3192525. doi:10.1016/S0021-9258(19)81321-2 .
- Chambers JC, Keene JD (1985). „Isolation and analysis of cDNA clones expressing human lupus La antigen.”. Proc. Natl. Acad. Sci. U.S.A. 82 (7): 2115—9. PMC 397503 . PMID 3856888. doi:10.1073/pnas.82.7.2115 .
- Svitkin YV, Pause A, Sonenberg N (1994). „La autoantigen alleviates translational repression by the 5' leader sequence of the human immunodeficiency virus type 1 mRNA.”. J. Virol. 68 (11): 7001—7. PMC 237137 . PMID 7933082. doi:10.1128/JVI.68.11.7001-7007.1994.
- Tröster, H.; Metzger, TE; Semsei, I. (1994). „One gene, two transcripts: isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjögrens' syndrome.”. J. Exp. Med. 180 (6): 2059—67. PMC 2191769 . PMID 7964483. doi:10.1084/jem.180.6.2059.
- Fan, H.; Sakulich, AL; Goodier, JL (1997). „Phosphorylation of the human La antigen on serine 366 can regulate recycling of RNA polymerase III transcription complexes.”. Cell. 88 (5): 707—15. PMID 9054510. S2CID 2223069. doi:10.1016/S0092-8674(00)81913-3.
- McLaren RS, Caruccio N, Ross J (1997). „Human La protein: a stabilizer of histone mRNA.”. Mol. Cell. Biol. 17 (6): 3028—36. PMC 232155 . PMID 9154801. doi:10.1128/MCB.17.6.3028.
- Grölz D, Bachmann M (1997). „The nuclear autoantigen La/SS-associated antigen B: one gene, three functional mRNAs.”. Biochem. J. 323 (1): 151—8. PMC 1218288 . PMID 9173875. doi:10.1042/bj3230151.
- Helsloot J, Sturgess A (1998). „T cell reactivity to Sjögren's syndrome related antigen La(SSB).”. J. Rheumatol. 24 (12): 2340—7. PMID 9415639.
- Broekhuis, CH; Neubauer, G.; van der Heijden A (2000). „Detailed analysis of the phosphorylation of the human La (SS-B) autoantigen. (De)phosphorylation does not affect its subcellular distribution.”. Biochemistry. 39 (11): 3023—33. PMID 10715123. doi:10.1021/bi992308c.
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- Intine, RV; Sakulich, AL; Koduru, SB (2000). „Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366.”. Mol. Cell. 6 (2): 339—48. PMID 10983981. doi:10.1016/S1097-2765(00)00034-4.
- Nashimoto, M.; C, Nashimoto; Tamura, M. (2001). „The inhibitory effect of the autoantigen La on in vitro 3' processing of mammalian precursor tRNAs.”. J. Mol. Biol. 312 (5): 975—84. PMID 11580243. doi:10.1006/jmbi.2001.5026.
- De Nova-Ocampo M, Villegas-Sepúlveda N, del Angel RM (2002). „Translation elongation factor-1alpha, La, and PTB interact with the 3' untranslated region of dengue 4 virus RNA.”. Virology. 295 (2): 337—47. PMID 12033793. doi:10.1006/viro.2002.1407.
- Intine RV, Dundr M, Misteli T, Maraia RJ (2002). „Aberrant nuclear trafficking of La protein leads to disordered processing of associated precursor tRNAs.”. Mol. Cell. 9 (5): 1113—23. PMID 12049746. doi:10.1016/S1097-2765(02)00533-6.
- Fouraux, MA; Bouvet, P.; S, Verkaart (2002). „Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes.”. J. Mol. Biol. 320 (3): 475—88. PMID 12096904. doi:10.1016/S0022-2836(02)00518-1.
Spoljašnje veze
uredi- UniProtKB - P05455 (LA_HUMAN) (jezik: engleski)
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