The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-κB, pyrin-only protein 4.
The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-κB, pyrin-only protein 4.
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CLRX.1/NOD24（NLRP2P）假元代码NF-κB的功能负调节剂，仅吡啶蛋白4。
DOI：
10.1038/gene.2014.30
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发表时间：
2014-09
影响因子：
5
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中科院分区：
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假基因是具有功能的亲本基因的复制但失效的副本。然而，一些假基因获得或保留了功能。在这项研究中，我们考虑了nlrp2相关的、高等灵长类特异性的加工假基因NLRP2P的功能作用，它与Pyrin-only蛋白2 （POP2/PYDC2）密切相关，后者是NF-κB和炎性体的调节因子。X染色体上的NLRP2P开放阅读框具有与加工假基因（反转录转座子）一致的特征，但编码一个45个氨基酸的pyrin结构域相关蛋白。NLRP2P的开放阅读框与POP2有80%的同源性，在东半球灵长类动物中处于净化选择状态。NLRP2P mRNA虽然广泛表达，但在人单核细胞中可被LPS上调。在功能上，NLRP2P通过降低激活RelA/p65的磷酸化而损害NF-κB p65的转激活。与POP2类似，NLRP2P在TLR刺激后减少NF-κ b依赖性细胞因子TNFα和IL-6的产生。与POP2相反，NLRP2P不能抑制asc依赖性NLRP3炎症小体。此外，除了调节细胞因子的产生，NLRP2P在细胞周期调节和细胞死亡中也有潜在的作用。总的来说，我们的研究结果表明NLRP2P是一个复活的加工假基因，它调节NF-κB RelA/p65的活性，因此代表了POP家族的最新成员POP4。
Pseudogenes are duplicated yet defunct copies of functional parent genes. However, some pseudogenes have gained or retained function. In this study we consider a functional role for the NLRP2-related, higher primate specific, processed pseudogene NLRP2P, which is closely related to Pyrin-only protein 2 (POP2/PYDC2), a regulator of NF-κB and the inflammasome. The NLRP2P open reading frame on chromosome X has features consistent with a processed pseudogene (retrotransposon), yet encodes a 45 amino acid, Pyrin-domain related protein. The open reading frame of NLRP2P shares 80% identity with POP2 and is under purifying selection across Old World primates. Although widely expressed, NLRP2P mRNA is upregulated by LPS in human monocytic cells. Functionally, NLRP2P impairs NF-κB p65 transactivation by reducing activating phosphorylation of RelA/p65. Reminiscent of POP2, NLRP2P reduces production of the NF-κB-dependent cytokines TNFα and IL-6 following TLR stimulation. In contrast to POP2, NLRP2P fails to inhibit the ASC-dependent NLRP3 inflammasome. In addition, beyond regulating cytokine production, NLRP2P has a potential role in cell cycle regulation and cell death. Collectively, our findings suggest that NLRP2P is a resurrected processed pseudogene that regulates NF-κB RelA/p65 activity and thus represents the newest member of the POP family, POP4.