Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation
Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation
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DOI：
10.1128/iai.01315-06
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发表时间：
2007-03-01
影响因子：
3.1
通讯作者：
Stehlik, Christian
中科院分区：
文献类型：
--
作者：
Dorfleutner, Andrea;Bryan, Nicole B.;Stehlik, Christian
吡啶结构域（PYD）蛋白最近通过激活炎症介体途径而成为针对细胞内病原体的先天免疫力涉及的重要信号分子。 ASC是中央适配器蛋白，它通过含PYD的病原体识别受体（称为PYD-NOD样受体（NLR），PAN，PAP，PYPAF，NALP，NALP，NOD和CATERPILLER蛋白）将病原体识别与下游效应子的激活，包括激活caspase-1和nf-kappaB。这些效应子的激活发生在特定蛋白复合物（称为特定蛋白质复合物）时发生形成炎症。 PYD信号转导导致炎症体组装和特定效应蛋白的激活。它由仅细胞PYD蛋白（CPOP1。）调节，该蛋白与ASC结合并干扰ASC募集到活化的PYD-NLRS。在这里，我们描述了第二个细胞POP（CPOP2）的识别和表征，该PAP（CPOP2）与PAN1的PYD显示出最高的同源性。 CPOP2与ASC和PAN1结合，从而阻止了冷冻蛋白和含PAN1的炎症体的形成，CASPASE-1的激活以及随后的生物活性Irthleukin-1 Beta的加工和分泌。第二个CPOP的存在提供了对炎症体形成的更多见解，并表明POP可能是“微调”含Pyd-NLR蛋白质蛋白质蛋白质炎症的活动的常见调节机制。
Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN, PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream effectors, including activation of caspase-1 and NF-kappa B. Activation of these effectors occurs when specific protein complexes, known as inflammasomes, are formed. PYD signal transduction leads to inflammasome assembly and activation of specific effector proteins. It is modulated by a cellular PYD-only protein (cPOP1.), which binds to ASC and interferes with the recruitment of ASC to activated PYD-NLRs. Here we describe the identification and characterization of a second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1. cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing and secretion of bioactive interleukin-1 beta. Existence of a second cPOP provides additional insights into inflammasome formation and suggests that POPs might be a common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR family protein-containing inflammasomes.