Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia
Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine i...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 13, 1999
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 1999, Volume: 96, Issue: 8, Pages: 4552-4557 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.96.8.4552 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.96.8.4552 Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/96/8/4552 
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| Author Notes: | David A. Martin, Lixin Zheng, Richard M. Siegel, Baohua Huang, Galen H. Fisher, Jin Wang, Christine E. Jackson, Jennifer M. Puck, Janet Dale, Stephen E. Straus, Marcus E. Peter, Peter H. Krammer, Stephen Fesik, and Michael J. Lenardo |
| Summary: | Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1. |
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| Item Description: | Gesehen am 23.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.96.8.4552 |