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Abstract:

The presence of additional N-glycans in the Fab region of IgG has shown to dramatically modify the properties and functionality of these molecules including changes in antibody affinity and stability. However, the underlying molecular mechanism responsible for the presence or absence of these glycans remains unknown. Polypeptide N-linked glycosylation is catalyzed in the lumen of the endoplasmic reticulum by the oligosaccharyltransferase complex. Mammalian cells can express two isoforms of the oligosaccharyltransferase catalytic subunit (STT3-A and STT3-B), which are endowed with distinct enzymatic properties. In this work we employed a murine hybridoma cell culture to study whether the expression of STT3 isoforms could be modulated by progesterone, thus altering the pattern of IgG N-glycosylation. We found that progesterone induces a switch of STT3 isoform expression, increasing IgG N-glycosylation. These effects were dependent on the progesterone-induced blocking factor (PIBF), whose concentration was modulated by progesterone. PIBF was previously found to be an immunomodulatory molecule relevant for the maintenance of pregnancy. We concluded that the STT3-B/STT3-A ratio modulates the N-glycosylation level of IgG, in agreement with previous data showing that full N-glycosylation of polypeptides requires cooperation between both catalytic isoforms. This work provides the first evidence that STT3 isoforms can be hormonally modulated, with marked consequences on IgG N-glycosylation. © 2011 Elsevier B.V.

Registro:

Documento: Artículo
Título:Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation
Autor:Prados, M.B.; La Blunda, J.; Szekeres-Bartho, J.; Caramelo, J.; Miranda, S.
Filiación:GlycoInmuno Biology Lab, Instituto de Investigaciones Cardiologicas Prof. Dr. Alberto C. Taquini (ININCA), CONICET-Universidad de Buenos Aires, Marcelo T. de Alvear 2270 2 piso, Ciudad Autonoma de Buenos Aires (C1122AAJ), Argentina
Department of Medical Microbiology and Immunology, Medical School, Pecs University, Szigeti ut 12, H-7624 Pecs, Hungary
Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), CONICET and Fundación Instituto Leloir, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Av. Patricias Argentinas 435, Ciudad de Buenos Aires (C1405BWE), Argentina
Palabras clave:IgG; IL-6; N-glycosylation; PIBF; Progesterone; STT3; cell protein; immunoglobulin G; isoenzyme; oligosaccharyltransferase; peptide derivative; polypeptide; progesterone; progesterone induced blocking factor; protein STT3; protein STT3 A; protein STT3 B; transferase; unclassified drug; animal cell; article; catalysis; controlled study; hybridoma cell culture; immunomodulation; mouse; nonhuman; pregnancy; priority journal; protein expression; protein glycosylation; protein protein interaction; Animals; Antibodies, Blocking; Dinitrophenols; Gene Expression Regulation; Glycosylation; Hexosyltransferases; Hybridomas; Immunoglobulin G; Immunomodulation; Membrane Proteins; Mice; Pregnancy Proteins; Progesterone; Protein Isoforms
Año:2011
Volumen:137
Número:1-2
Página de inicio:28
Página de fin:37
DOI: http://dx.doi.org/10.1016/j.imlet.2011.01.017
Título revista:Immunology Letters
Título revista abreviado:Immunol. Lett.
ISSN:01652478
CODEN:IMLED
CAS:immunoglobulin G, 97794-27-9; progesterone, 57-83-0; transferase, 9047-61-4; Antibodies, Blocking; Dinitrophenols; Hexosyltransferases, 2.4.1.-; Immunoglobulin G; Membrane Proteins; Pibf1 protein, mouse; Pregnancy Proteins; Progesterone, 57-83-0; Protein Isoforms; dolichyl-diphosphooligosaccharide - protein glycotransferase, 2.4.1.119
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01652478_v137_n1-2_p28_Prados

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Citas:

---------- APA ----------
Prados, M.B., La Blunda, J., Szekeres-Bartho, J., Caramelo, J. & Miranda, S. (2011) . Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation. Immunology Letters, 137(1-2), 28-37.
http://dx.doi.org/10.1016/j.imlet.2011.01.017
---------- CHICAGO ----------
Prados, M.B., La Blunda, J., Szekeres-Bartho, J., Caramelo, J., Miranda, S. "Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation" . Immunology Letters 137, no. 1-2 (2011) : 28-37.
http://dx.doi.org/10.1016/j.imlet.2011.01.017
---------- MLA ----------
Prados, M.B., La Blunda, J., Szekeres-Bartho, J., Caramelo, J., Miranda, S. "Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation" . Immunology Letters, vol. 137, no. 1-2, 2011, pp. 28-37.
http://dx.doi.org/10.1016/j.imlet.2011.01.017
---------- VANCOUVER ----------
Prados, M.B., La Blunda, J., Szekeres-Bartho, J., Caramelo, J., Miranda, S. Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation. Immunol. Lett. 2011;137(1-2):28-37.
http://dx.doi.org/10.1016/j.imlet.2011.01.017