Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation
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 glycan...
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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01652478_v137_n1-2_p28_Prados http://hdl.handle.net/20.500.12110/paper_01652478_v137_n1-2_p28_Prados |
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paper:paper_01652478_v137_n1-2_p28_Prados2023-06-08T15:14:50Z Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation 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 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. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01652478_v137_n1-2_p28_Prados http://hdl.handle.net/20.500.12110/paper_01652478_v137_n1-2_p28_Prados |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| topic_facet |
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 |
| description |
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. |
| title |
Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| title_short |
Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| title_full |
Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| title_fullStr |
Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| title_full_unstemmed |
Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation |
| title_sort |
progesterone induces a switch in oligosaccharyltransferase isoform expression: consequences on igg n-glycosylation |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01652478_v137_n1-2_p28_Prados http://hdl.handle.net/20.500.12110/paper_01652478_v137_n1-2_p28_Prados |
| _version_ |
1768545826774188032 |