Induction of apoptosis and activation of NF-κB by CD95 require different signalling thresholds
Mutations in the death domain of the death receptor CD95 (APO‐1/Fas) cause lymphoproliferation and autoimmune disease in both lprcg mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozyg...
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Published in | EMBO reports Vol. 5; no. 11; pp. 1084 - 1089 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.11.2004
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Subjects | |
Online Access | Get full text |
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Summary: | Mutations in the death domain of the death receptor CD95 (APO‐1/Fas) cause lymphoproliferation and autoimmune disease in both lprcg mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lprcg mice and coexpressing wild‐type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild‐type alleles of CD95. By contrast, nuclear factor‐κB (NF‐κB) can be fully activated in cells expressing both a mutant and a wild‐type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95‐mediated apoptosis but normal activation of NF‐κB when compared with wild‐type mice. Mutations in CD95 may eliminate the tumour‐suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients. |
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Bibliography: | ark:/67375/WNG-WX0749JR-Z istex:87CD8FC545824E69413E9FBE61297899F26CFB4F ArticleID:EMBR7400280 Supplementary Figure 1Supplementary Figure 2 |
ISSN: | 1469-221X 1469-3178 |
DOI: | 10.1038/sj.embor.7400280 |