The ubiquitin-like protein FAT10 forms covalent conjugates and induces apoptosis
The ubiquitin-like protein FAT10 forms covalent conjugates and induces apoptosis
复制标题
DOI：
10.1074/jbc.m105139200
复制
发表时间：
2001-09-21
影响因子：
4.8
通讯作者：
Groettrup, M
中科院分区：
文献类型：
--
作者：
Raasi, S;Schmidtke, G;Groettrup, M
FAT 10是一种泛素样蛋白，在主要组织相容性复合体I类基因座中编码，并与干扰素-γ和肿瘤坏死因子α协同诱导。该分子由两个串联排列的泛素样结构域组成，并且在其羧基末端具有保守的双甘氨酸基序，该基序通常用于泛素样蛋白质中用于与缀合蛋白质的异肽连接。我们通过在小鼠成纤维细胞中以四环素可抑制的方式表达血凝素标记的野生型形式以及二甘氨酸缺陷突变体形式的小鼠FAT 10来研究FAT 10的功能。FAT 10表达不影响主要组织相容性复合体I类细胞表面表达或抗原呈递。然而，我们发现，野生型，而不是突变体FAT 10在24小时内诱导凋亡的半胱天冬酶依赖的方式所示的膜联蛋白V细胞表面染色和DNA片段。野生型FAT 10，但不是它的双甘氨酸突变体，共价结合到迄今未鉴定的蛋白质，表明特定的FAT 10激活和结合酶必须在未刺激的成纤维细胞中起作用。由于FAT 10表达引起细胞凋亡，并且可由肿瘤坏死因子α诱导，因此它可能在功能上参与由该细胞因子介导的程序性细胞死亡。
FAT10 is a ubiquitin-like protein that is encoded in the major histocompatibility complex class I locus and is synergistically inducible with interferon-gamma and tumor necrosis factor alpha. The molecule consists of two ubiquitin-like domains in tandem arrangement and bears a conserved diglycine motif at its carboxyl terminus commonly used in ubiquitin-like proteins for isopeptide linkage to conjugated proteins. We investigated the function of FAT10 by expressing murine FAT10 in a hemagglutinin-tagged wild type form as well as a diglycine-deficient mutant form in mouse fibroblasts in a tetracycline-repressible manner. FAT10 expression did not affect major histocompatibility complex class I cell surface expression or antigen presentation. However, we found that wild type but not mutant FAT10 caused apoptosis within 24 h of induction in a caspase-dependent manner as indicated by annexin V cell surface staining and DNA fragmentation. Wild type FAT10, but not its diglycine mutant, was covalently conjugated to thus far unidentified proteins, indicating that specific FAT10 activating and conjugating enzymes must be operative in unstimulated fibroblasts. Because FAT10 expression causes apoptosis and is inducible with tumor necrosis factor alpha, it may be functionally involved in the programmed cell death mediated by this cytokine.