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Ssb  -  Sjogren syndrome antigen B

Mus musculus

Synonyms: La autoantigen homolog, La protein, La ribonucleoprotein, Lupus La protein homolog, SS-B, ...
 
 
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Disease relevance of Ssb

  • The La protein is a target of autoantibodies in patients suffering from Sjögren's syndrome, systemic lupus erythematosus, and neonatal lupus [1].
  • OBJECTIVE: In isolated congenital heart block, the mechanism by which maternal autoantibodies target the intracellular components of the Ro/La RNP complex is unclear [2].
  • Originally described as an autoantigen in patients with rheumatic disease, the La protein binds to newly synthesized RNA polymerase III transcripts [3].
  • The larger blebs (apoptotic bodies) contain nucleosomal DNA, Ro, La, and the small nuclear ribonucleoproteins [4].
  • OBJECTIVE: To determine whether La and/or Ro epitopes on apoptotic cells in fetal organs that are targeted in neonatal lupus syndrome (NLS) are accessible for binding by autoantibodies in vivo, we traced the fate of transplacental autoantibodies in a murine passive transfer model [5].
 

Psychiatry related information on Ssb

  • Thus, following immunization, in addition to 16/6 Id+ antibodies, the mice produced antibodies to various nuclear antigens: single-stranded DNA, double-stranded DNA, poly(I), poly(G), Ro, La, Sm and ribonucleoproteins [6].
 

High impact information on Ssb

  • The La protein from calf thymus was separated into RNA binding and nonbinding subclasses [7].
  • La protein was able to melt a synthetic DNA-RNA hybrid in a reaction that required ATP hydrolysis [7].
  • The human leukocyte antigen (HLA) locus DQ is related to the primary Sjögren's syndrome autoantibodies that bind the RNA proteins Ro/SSA and La/SSB [8].
  • Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice [9].
  • In contrast, immunization with the subdominant mouse La13-30 determinant induced a proliferative T cell response associated with the appearance of specific autoantibodies recognizing multiple intrastructural (La) and intermolecular components (Ro) of the murine La/Ro RNP [9].
 

Biological context of Ssb

  • Analogous experiments using recombinant mRo60 fragments spanning the mRo60 molecule revealed a similar pattern of oligoclonality in the specificity of anti-Ro60 autoimmunity following active immunization with La and Ro52 [10].
  • Intramolecular spreading of the anti-La antibody response was further demonstrated by the appearance of autoantibodies to multiple, nonoverlapping antigenic regions of La, after immunization of mice with the 107-aa La A subfragment [11].
  • We have tested the extent of immune self-tolerance to the ubiquitously expressed nuclear/cytoplasmic autoantigens La (SS-B) and Ro (SS-A) in healthy, nonautoimmune mice [11].
  • In addition, the data reveal the incomplete nature of immune tolerance to La and Ro despite their endogenous expression in all nucleated cells [11].
  • La also associates with a class of mRNAs that encode ribosome subunits and precursors to snoRNAs involved in ribosome biogenesis [1].
 

Anatomical context of Ssb

  • Although the immune response to the immunizing antigen is polyclonal and diversified, little is known about the specificity of the recruited autoimmune responses to the endogenous Ro and La antigens which drive B-cell spreading [10].
  • The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells [1].
  • La-/- offspring were detected at the expected frequency among blastocysts prior to implantation, whereas no nullizygotes were detected after implantation, indicating that La is required early in development [1].
  • Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B) [12].
  • Two yeast La motif-containing proteins are RNA-binding proteins that associate with polyribosomes [3].
 

Associations of Ssb with chemical compounds

  • The few transcripts synthesized in the absence of La have fewer uridylate residues at their 3' ends than those made in its presence [13].
  • Isofocusing in granulated gels separated intact uridylic acid (U)-snRNPs from tRNA and La RNPs [14].
  • These monoclonal antibodies were found to bind to nucleic acid as well as non-nucleic acid antigens, such as beta-galactosidase, cardiolipin, Ro, La and Sm [15].
  • However, they failed to react with either an N-terminal La peptide consisting of amino acids 1-192 or a C-terminal La peptide starting at methionine 223, while they still reacted with recombinant La peptides consisting of the amino acids 1-341 or starting at 192 [16].
  • That trichloracetic acid (TCA)-soluble products of 125I SS-B appeared in plasma within 1 min of iv injection suggests rapid in vivo breakdown [17].
 

Enzymatic interactions of Ssb

  • Several lines of evidence show that La protein is cleaved by caspase-3 or closely related proteases at Asp-374 in the COOH terminus [18].
 

Other interactions of Ssb

  • Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides [12].
  • We were able to HNE-modify various antigens (BSA, the autoantigens Ro, La and Sm/nRNP, 60 kDa Ro and Sm MAPs) using this procedure [19].
 

Analytical, diagnostic and therapeutic context of Ssb

  • High-resolution confocal microscopy revealed that in cells that had undergone apoptosis, La antigen asymmetrically clustered near the surface of TUNEL-positive nuclei and apoptotic bodies [2].
  • Binding of human autoantibodies to purified human, mouse, and bovine recombinant fragments representing immunodominant regions of the La/SS-B polypeptide was compared using Western blotting and ELISA [20].
  • The Ro RNPs are quite stable and are localized by immunofluorescence in the cell cytoplasm, whereas the majority of the La RNPs turn over rapidly and reside in the nucleus [21].
  • Although some La mutants altered in a C-terminal basic region bind RNA in mobility shift assays, they are defective in RNA 3'-end protection and do not support transcription, while one C-terminal substitution mutant is defective only in transcription [22].
  • Fine specificities of autoantibodies directed against the Ro, La, Sm, RNP, and Jo-1 proteins defined by two-dimensional gel electrophoresis and immunoblotting [23].

References

  1. The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells. Park, J.M., Kohn, M.J., Bruinsma, M.W., Vech, C., Intine, R.V., Fuhrmann, S., Grinberg, A., Mukherjee, I., Love, P.E., Ko, M.S., DePamphilis, M.L., Maraia, R.J. Mol. Cell. Biol. (2006) [Pubmed]
  2. Subcellular redistribution of la/SSB autoantigen during physiologic apoptosis in the fetal mouse heart and conduction system: a clue to the pathogenesis of congenital heart block. Tran, H.B., Ohlsson, M., Beroukas, D., Hiscock, J., Bradley, J., Buyon, J.P., Gordon, T.P. Arthritis Rheum. (2002) [Pubmed]
  3. Two yeast La motif-containing proteins are RNA-binding proteins that associate with polyribosomes. Sobel, S.G., Wolin, S.L. Mol. Biol. Cell (1999) [Pubmed]
  4. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. Casciola-Rosen, L.A., Anhalt, G., Rosen, A. J. Exp. Med. (1994) [Pubmed]
  5. Anti-La/SSB antibodies transported across the placenta bind apoptotic cells in fetal organs targeted in neonatal lupus. Tran, H.B., Macardle, P.J., Hiscock, J., Cavill, D., Bradley, J., Buyon, J.P., Gordon, T.P. Arthritis Rheum. (2002) [Pubmed]
  6. The role of anti-idiotypic antibodies in the induction of experimental systemic lupus erythematosus in mice. Mendlovic, S., Fricke, H., Shoenfeld, Y., Mozes, E. Eur. J. Immunol. (1989) [Pubmed]
  7. Characterization of the autoantigen La as a nucleic acid-dependent ATPase/dATPase with melting properties. Bachmann, M., Pfeifer, K., Schröder, H.C., Müller, W.E. Cell (1990) [Pubmed]
  8. Gene interaction at HLA-DQ enhances autoantibody production in primary Sjögren's syndrome. Harley, J.B., Reichlin, M., Arnett, F.C., Alexander, E.L., Bias, W.B., Provost, T.T. Science (1986) [Pubmed]
  9. Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice. Reynolds, P., Gordon, T.P., Purcell, A.W., Jackson, D.C., McCluskey, J. J. Exp. Med. (1996) [Pubmed]
  10. Restricted specificity of intermolecular spreading to endogenous La (SS-B) and 60 kDa Ro (SS-A) in experimental autoimmunity. Gordon, T.P., Kinoshita, G., Cavill, D., Keech, C., Farris, A., Kaufman, K., McCluskey, J., Purcell, A. Scand. J. Immunol. (2002) [Pubmed]
  11. Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A). Topfer, F., Gordon, T., McCluskey, J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  12. Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B). Farris, A.D., Brown, L., Reynolds, P., Harley, J.B., James, J.A., Scofield, R.H., McCluskey, J., Gordon, T.P. J. Immunol. (1999) [Pubmed]
  13. The RNA binding protein La influences both the accuracy and the efficiency of RNA polymerase III transcription in vitro. Gottlieb, E., Steitz, J.A. EMBO J. (1989) [Pubmed]
  14. Isofocusing of antigenic small nuclear ribonucleoproteins. II. Preparative isolation. Schrier, W.H., Feinbaum, R., Okarma, T.B. Anal. Biochem. (1985) [Pubmed]
  15. The fine specificity of monoclonal anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. Pyun, E.H., Pisetsky, D.S., Gilkeson, G.S. J. Autoimmun. (1993) [Pubmed]
  16. Cross-reactivity of antibodies immunoadsorbed to laminin with recombinant human La (SS-B) protein. Chang, S.H., Huh, M.S., Kim, H.R., Kim, I.S., Kim, S., Lee, J.S., Semsei, I., Grölz, D., Bachmann, M. J. Autoimmun. (1998) [Pubmed]
  17. Tissue uptake and catabolic studies of 125I SS-B (La) injected into mice. Schrieber, L., Melsom, R.D., Venables, P.J., Maini, R.N. Clin. Immunol. Immunopathol. (1984) [Pubmed]
  18. La autoantigen is cleaved in the COOH terminus and loses the nuclear localization signal during apoptosis. Ayukawa, K., Taniguchi, S., Masumoto, J., Hashimoto, S., Sarvotham, H., Hara, A., Aoyama, T., Sagara, J. J. Biol. Chem. (2000) [Pubmed]
  19. In vitro modification of solid phase multiple antigenic peptides/autoantigens with 4-hydroxy-2-nonenal (HNE) provide ideal substrates for detection of anti-HNE antibodies and peptide antioxidants. Kurien, B.T., Hal Scofield, R. J. Immunol. Methods (2005) [Pubmed]
  20. Identification of a human-specific epitope in a conserved region of the La/SS-B autoantigen. Weng, Y.M., McNeilage, J., Topfer, F., McCluskey, J., Gordon, T. J. Clin. Invest. (1993) [Pubmed]
  21. Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Hendrick, J.P., Wolin, S.L., Rinke, J., Lerner, M.R., Steitz, J.A. Mol. Cell. Biol. (1981) [Pubmed]
  22. A carboxy-terminal basic region controls RNA polymerase III transcription factor activity of human La protein. Goodier, J.L., Fan, H., Maraia, R.J. Mol. Cell. Biol. (1997) [Pubmed]
  23. Fine specificities of autoantibodies directed against the Ro, La, Sm, RNP, and Jo-1 proteins defined by two-dimensional gel electrophoresis and immunoblotting. Elkon, K.B., Jankowski, P.W. J. Immunol. (1985) [Pubmed]
 
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