Inohara N, Koseki T, del Peso L, Hu Y, Yee C, Chen S, Carrio R, Merino J, Liu D, Ni J, Núñez G
Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
J Biol Chem. 1999 May 21;274(21):14560-7. doi: 10.1074/jbc.274.21.14560.
Ced-4 and Apaf-1 belong to a major class of apoptosis regulators that contain caspase-recruitment (CARD) and nucleotide-binding oligomerization domains. Nod1, a protein with an NH2-terminal CARD-linked to a nucleotide-binding domain and a COOH-terminal segment with multiple leucine-rich repeats, was identified. Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase-9-induced apoptosis. As reported for Apaf-1, Nod1 required both the CARD and P-loop for function. Unlike Apaf-1, Nod1 induced activation of nuclear factor-kappa-B (NF-kappaB) and bound RICK, a CARD-containing kinase that also induces NF-kappaB activation. Nod1 mutants inhibited NF-kappaB activity induced by RICK, but not that resulting from tumor necrosis factor-alpha stimulation. Thus, Nod1 is a leucine-rich repeat-containing Apaf-1-like molecule that can regulate both apoptosis and NF-kappaB activation pathways.
Ced-4和Apaf-1属于一类主要的凋亡调节因子，它们含有半胱天冬酶募集结构域（CARD）和核苷酸结合寡聚化结构域。Nod1是一种蛋白质，其氨基末端CARD与核苷酸结合结构域相连，羧基末端有多个富含亮氨酸的重复序列。研究发现，Nod-1能与多个具有长前结构域的半胱天冬酶结合，但能特异性激活半胱天冬酶-9并促进半胱天冬酶-9诱导的细胞凋亡。正如对Apaf-1的报道，Nod1发挥功能需要CARD和P环。与Apaf-1不同，Nod1能诱导核因子-κB（NF-κB）激活，并与RICK结合，RICK是一种含CARD的激酶，也能诱导NF-κB激活。Nod1突变体可抑制RICK诱导的NF-κB活性，但不抑制肿瘤坏死因子-α刺激所导致的NF-κB活性。因此，Nod1是一种含富含亮氨酸重复序列的类似Apaf-1的分子，可同时调节细胞凋亡和NF-κB激活途径。
