Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation
Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of...
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| Veröffentlicht in: | PloS one 2011-05, Vol.6 (5), p.e19927-e19927 |
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| creator | Shatnyeva, Olga M Kubarenko, Andriy V Weber, Claudia E M Pappa, Alexander Schwartz-Albiez, Reinhard Weber, Alexander N R Krammer, Peter H Lavrik, Inna N |
| description | Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems. |
| doi_str_mv | 10.1371/journal.pone.0019927 |
| format | Article |
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It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0019927</identifier><identifier>PMID: 21625644</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Analysis ; APO-1 protein ; Apoptosis ; Bacteria ; Biology ; Blotting, Western ; Cancer ; Caspase 8 - metabolism ; CD95 antigen ; Cells, Cultured ; Cellular signal transduction ; Cholera toxin ; Computational Biology ; Cytochrome ; Death Domain Receptor Signaling Adaptor Proteins ; Deglycosylation ; Enzyme-Linked Immunosorbent Assay ; Fas antigen ; fas Receptor - chemistry ; fas Receptor - genetics ; fas Receptor - metabolism ; Flow Cytometry ; Glycosylation ; Humans ; Immunoprecipitation ; Ligands ; Lymphocytes - cytology ; Lymphocytes - metabolism ; Medical research ; Modulation ; Mutagenesis ; Mutants ; Mutation - genetics ; Protein Conformation ; Proteins ; Signal Transduction ; Signaling ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; TRAIL protein ; Tumor necrosis factor-TNF ; Waterborne diseases</subject><ispartof>PloS one, 2011-05, Vol.6 (5), p.e19927-e19927</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Shatnyeva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Shatnyeva et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-2d5b37effc4b32c50f93ee6a33861e84029dd4f57d432ea825d0c78756cc93103</citedby><cites>FETCH-LOGICAL-c757t-2d5b37effc4b32c50f93ee6a33861e84029dd4f57d432ea825d0c78756cc93103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097226/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097226/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21625644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pastore, Annalisa</contributor><creatorcontrib>Shatnyeva, Olga M</creatorcontrib><creatorcontrib>Kubarenko, Andriy V</creatorcontrib><creatorcontrib>Weber, Claudia E M</creatorcontrib><creatorcontrib>Pappa, Alexander</creatorcontrib><creatorcontrib>Schwartz-Albiez, Reinhard</creatorcontrib><creatorcontrib>Weber, Alexander N R</creatorcontrib><creatorcontrib>Krammer, Peter H</creatorcontrib><creatorcontrib>Lavrik, Inna N</creatorcontrib><title>Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems.</description><subject>Activation</subject><subject>Analysis</subject><subject>APO-1 protein</subject><subject>Apoptosis</subject><subject>Bacteria</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Caspase 8 - metabolism</subject><subject>CD95 antigen</subject><subject>Cells, Cultured</subject><subject>Cellular signal transduction</subject><subject>Cholera toxin</subject><subject>Computational Biology</subject><subject>Cytochrome</subject><subject>Death Domain Receptor Signaling Adaptor Proteins</subject><subject>Deglycosylation</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fas antigen</subject><subject>fas Receptor - chemistry</subject><subject>fas Receptor - genetics</subject><subject>fas Receptor - metabolism</subject><subject>Flow Cytometry</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Ligands</subject><subject>Lymphocytes - cytology</subject><subject>Lymphocytes - metabolism</subject><subject>Medical research</subject><subject>Modulation</subject><subject>Mutagenesis</subject><subject>Mutants</subject><subject>Mutation - genetics</subject><subject>Protein Conformation</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>TNF-Related Apoptosis-Inducing Ligand - metabolism</subject><subject>TRAIL protein</subject><subject>Tumor necrosis factor-TNF</subject><subject>Waterborne diseases</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkluLEzEYhgdR3HX1H4gWBMWLqTln4oWw1FNldcHTbUhzaFPSyTiZEfvvzWxnl47sheQiId_zvkm-vEXxGII5xBy-2sa-rVWYN7G2cwCgEIjfKU6hwKhkCOC7R-uT4kFKWwAorhi7X5wgyBBlhJwWnz5H0wfV-VjPopt1GztbvBW09LXptTUz1cSmi8mn11e1NgY7cAMz-1Kuw17HtD_oHxb3nArJPhrns-LH-3ffFx_Li8sPy8X5Rak55V2JDF1hbp3TZIWRpsAJbC1TON8N2ooAJIwhjnJDMLKqQtQAzStOmdYCQ4DPiqcH3ybEJMc2JAmRyGVYgYFYHggT1VY2rd-pdi-j8vJqI7ZrqdrO62CloogbBRHBpCIQsBV1K64xcNYqo4nOXm_G0_rVzhpt665VYWI6rdR-I9fxt8RAcIRYNngxGrTxV29TJ3c-aRuCqm3sk6yYoFXFOcrks3_I2x83UmuV7-9rF_OxevCU54SzSkBEeabmt1B5GLvzOkfG-bw_EbycCDLT2T_dWvUpyeW3r__PXv6css-P2I1VodukGPohMWkKkgOo25hSa91NjyGQQ-KvuyGHxMsx8Vn25Ph_bkTXEcd_AcCf-Uc</recordid><startdate>20110518</startdate><enddate>20110518</enddate><creator>Shatnyeva, Olga M</creator><creator>Kubarenko, Andriy V</creator><creator>Weber, Claudia E M</creator><creator>Pappa, Alexander</creator><creator>Schwartz-Albiez, Reinhard</creator><creator>Weber, Alexander N R</creator><creator>Krammer, Peter H</creator><creator>Lavrik, Inna N</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110518</creationdate><title>Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation</title><author>Shatnyeva, Olga M ; Kubarenko, Andriy V ; Weber, Claudia E M ; Pappa, Alexander ; Schwartz-Albiez, Reinhard ; Weber, Alexander N R ; Krammer, Peter H ; Lavrik, Inna N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-2d5b37effc4b32c50f93ee6a33861e84029dd4f57d432ea825d0c78756cc93103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Activation</topic><topic>Analysis</topic><topic>APO-1 protein</topic><topic>Apoptosis</topic><topic>Bacteria</topic><topic>Biology</topic><topic>Blotting, Western</topic><topic>Cancer</topic><topic>Caspase 8 - metabolism</topic><topic>CD95 antigen</topic><topic>Cells, Cultured</topic><topic>Cellular signal transduction</topic><topic>Cholera toxin</topic><topic>Computational Biology</topic><topic>Cytochrome</topic><topic>Death Domain Receptor Signaling Adaptor Proteins</topic><topic>Deglycosylation</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fas antigen</topic><topic>fas Receptor - chemistry</topic><topic>fas Receptor - genetics</topic><topic>fas Receptor - metabolism</topic><topic>Flow Cytometry</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Ligands</topic><topic>Lymphocytes - cytology</topic><topic>Lymphocytes - metabolism</topic><topic>Medical research</topic><topic>Modulation</topic><topic>Mutagenesis</topic><topic>Mutants</topic><topic>Mutation - genetics</topic><topic>Protein Conformation</topic><topic>Proteins</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>TNF-Related Apoptosis-Inducing Ligand - 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It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21625644</pmid><doi>10.1371/journal.pone.0019927</doi><tpages>e19927</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Analysis APO-1 protein Apoptosis Bacteria Biology Blotting, Western Cancer Caspase 8 - metabolism CD95 antigen Cells, Cultured Cellular signal transduction Cholera toxin Computational Biology Cytochrome Death Domain Receptor Signaling Adaptor Proteins Deglycosylation Enzyme-Linked Immunosorbent Assay Fas antigen fas Receptor - chemistry fas Receptor - genetics fas Receptor - metabolism Flow Cytometry Glycosylation Humans Immunoprecipitation Ligands Lymphocytes - cytology Lymphocytes - metabolism Medical research Modulation Mutagenesis Mutants Mutation - genetics Protein Conformation Proteins Signal Transduction Signaling TNF-Related Apoptosis-Inducing Ligand - metabolism TRAIL protein Tumor necrosis factor-TNF Waterborne diseases |
| title | Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation |
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