PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1
PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1
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DOI：
10.1093/intimm/dxh081
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Wang, YT;Hasegawa, M;Suda, T
最近，一个大的亚家族的核苷酸结合和寡聚化结构域的蛋白质，具有N-末端的pyrin-like结构域和C-末端的亮氨酸丰富的重复序列已被描述。在这项研究中，我们确定了PYNOD，这个家族的一个新成员，缺乏富含亮氨酸的重复序列。我们发现人PYNOD mRNA在各种组织中表达，并且在心脏、骨骼肌和脑中以高水平表达。它也在各种细胞系中表达，包括造血细胞系。PYNOD寡聚化并结合ASC（一种在细胞凋亡和炎症信号转导中起作用的衔接蛋白）以及caspase-1和IL-1 β。PYNOD抑制包含CARD（ASC）介导的NF-κ B活化和凋亡的凋亡相关斑点样蛋白，以及caspase-1介导的IL-1 β成熟，并且在存在和不存在CARD 12和PYPAF 1的组成型活性突变体（这些过程的增强子）的情况下都能抑制上述作用。因此，PYNOD是一种新型的细胞凋亡和炎症调节因子。
Recently, a large subfamily of nucleotide-binding and oligomerization domain-containing proteins that have an N-terminal pyrin-like domain and C-terminal leucine-rich repeats has been described. In this study, we identified PYNOD, a novel member of this family that lacks the leucine-rich repeats. We found that human PYNOD mRNA is expressed in various tissues and at high levels in heart, skeletal muscle and brain. It is also expressed in various cell lines, including haematopoietic cell lines. PYNOD oligomerizes and binds to ASC, an adaptor protein that plays a role in apoptotic and inflammatory signal transduction, and to caspase-1 and IL-1beta. PYNOD inhibits apoptosis-associated speck-like protein containing a CARD (ASC)-mediated NF-kappaB activation and apoptosis, and caspase-1-mediated IL-1beta maturation, and it does so in the presence and absence of constitutively active mutants of CARD12 and PYPAF1, which are enhancers of these processes. Thus, PYNOD is a novel regulator of apoptosis and inflammation.