Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations
Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations
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DOI：
10.1126/science.288.5475.2354
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发表时间：
2000-06-30
期刊：
影响因子：
56.9
通讯作者：
Lenardo, MJ
中科院分区：
文献类型：
--
作者：
Siegel, RM;Frederiksen, JK;Lenardo, MJ
编码死亡受体Fas异常形式的杂合突变主要干扰人类自身免疫性淋巴增生综合征中Fas诱导的淋巴细胞凋亡。这种效应，而不是依赖于配体诱导的受体寡聚化，被发现源于野生型和突变型Fas受体通过细胞外结构域中的特定区域的配体独立的相互作用。通过绿色荧光蛋白变体之间的荧光共振能量转移，在活细胞中发现了预缔合的Fas复合物。这些结果表明，形成的preassociated受体复合物是必要的Fas信号和显性干扰人类疾病。
Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced Lymphocyte apoptosis in human autoimmune Lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand-independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.