Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1
Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1
复制标题
DOI：
10.1074/jbc.c100250200
复制
发表时间：
2001-07-27
影响因子：
4.8
通讯作者：
Alnemri, ES
中科院分区：
文献类型：
--
作者：
Poyet, JL;Srinivasula, SM;Alnemri, ES
Procaspase-9含有一个NH 2-末端caspase相关的募集结构域（CARD），这是与Apaf-1直接关联和激活所必需的。Procaspase-1也含有一个NH 2-末端CARD结构域，这表明它的激活机制与procaspase-9一样，涉及与Apaf-1相关分子的结合。在这里，我们描述了人类Apaf-1相关蛋白，命名为Ipaf，含有一个NH 2-末端CARD结构域，一个中央核苷酸结合结构域，和一个COOH-末端调节亮氨酸丰富的重复结构域（LRR）的鉴定。Ipaf通过CARD-CARD相互作用与procaspase-1的CARD结构域直接特异性结合。缺乏其COOH末端LRR结构域的组成型活性Ipaf可以诱导转染细胞中的procaspase-1和caspase-1依赖性凋亡的自催化加工和活化。我们的研究结果表明，Ipaf是一个特定的和直接的激活caspase-1，并可能参与激活caspase-1的促炎和凋亡刺激。
Procaspase-9 contains an NH2-terminal caspase-associated recruitment domain (CARD), which is essential for direct association with Apaf-1 and activation. Procaspase-1 also contains an NH2-terminal CARD domain, suggesting that its mechanism of activation, like that of procaspase-9, involves association with an Apaf-1-related molecule. Here we describe the identification of a human Apaf-1-related protein, named Ipaf that contains an NH2-terminal CARD domain, a central nucleotide-binding domain, and a COOH-terminal regulatory leucine-rich repeat domain (LRR). Ipaf associates directly and specifically with the CARD domain of procaspase-1 through CARD-CARD interaction. A constitutively active Ipaf lacking its COOH-terminal LRR domain can induce autocatalytic processing and activation of procaspase-1 and caspase-1-dependent apoptosis in transfected cells. Our results suggest that Ipaf is a specific and direct activator of procaspase-1 and could be involved in activation of caspase-1 in response to pro-inflammatory and apoptotic stimuli.