The molecular interaction of Fas and FAP-1 - A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis
The molecular interaction of Fas and FAP-1 - A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis
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DOI：
10.1074/jbc.272.13.8539
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发表时间：
1997-03-28
影响因子：
4.8
通讯作者：
Sato, T
中科院分区：
文献类型：
--
作者：
Yanagisawa, J;Takahashi, M;Sato, T
Fas （APO-1/CD95）是肿瘤坏死因子受体超家族成员，是一种诱导细胞凋亡的细胞表面受体。一种蛋白酪氨酸磷酸酶，Fas相关磷酸酶-1 (Fas-associated phosphatase- 1, Fas- 1)，先前被确定为Fas结合蛋白，与Fas受体调节结构域的c端15个氨基酸相互作用。为了确定与FAP-1结合所需的Fas c末端的最小区域，我们使用一系列合成肽以及酵母双杂交系统筛选的随机肽库进行了Fas/FAP-1结合的体外抑制实验。结果表明，人Fas的c端3个氨基酸（SLV）是与FAP-1的第三个PDZ （GLGF）结构域相互作用的必要和充分条件。此外，直接细胞质显微注射这种三肽（Ac-SLV）导致Fas介导的凋亡在表达Fas和FAP-1的结肠癌细胞系中诱导。由于其他几种受体C末端的t(S/ t)X（V/L/I）基序已被证明与信号转导分子中的PDZ结构域相互作用，这可能代表了具有重要生物学功能的蛋白质-蛋白质相互作用的一般基序。
Fas (APO-1/CD95), which isa member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-l (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.