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一种新型蛋白质——小泛素样修饰蛋白对Fas/APO-1和肿瘤坏死因子介导的细胞死亡的保护作用

Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin.

作者信息

Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei C F, Chang H M, Yeh E T

机构信息

Division of Molecular Medicine, The University of Texas-Houston Health Science Center 77030, USA.

出版信息

J Immunol. 1996 Nov 15;157(10):4277-81.

PMID:8906799
Abstract

Fas/APO-1 and TNF receptor 1 share a common signaling motif in their cytoplasmic tail called the "death domain." Using the death domain as bait in the yeast two-hybrid system, several death domain-containing proteins that participate in cell death signaling have been identified. Here we report the isolation of a novel protein, sentrin, which interacts with Fas/APO-1 and TNF receptor 1 but not with FADD/MORT1 or CD40. Two-hybrid interaction assays reveal that sentrin associates only with the signal-competent forms of Fas/APO-1 or TNF receptor 1 death domains. Sentrin is a novel protein of 101 amino acids with homology to ubiquitin, Nedd8, and a Saccharomyces cerevisiae protein, Smt3. When overexpressed, sentrin provides protection against both anti-Fas/APO-1 and TNF-induced cell death.

摘要

Fas/APO-1和肿瘤坏死因子受体1在其细胞质尾部共享一个称为“死亡结构域”的共同信号基序。利用死亡结构域作为酵母双杂交系统中的诱饵,已鉴定出几种参与细胞死亡信号传导的含死亡结构域的蛋白质。在此,我们报告了一种新型蛋白质——泛素样蛋白(sentrin)的分离,它与Fas/APO-1和肿瘤坏死因子受体1相互作用,但不与FADD/MORT1或CD40相互作用。双杂交相互作用分析表明,泛素样蛋白仅与Fas/APO-1或肿瘤坏死因子受体1死亡结构域的信号活性形式相关联。泛素样蛋白是一种由101个氨基酸组成的新型蛋白质,与泛素、Nedd8和酿酒酵母蛋白Smt3具有同源性。当过度表达时,泛素样蛋白可提供针对抗Fas/APO-1和肿瘤坏死因子诱导的细胞死亡的保护作用。

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