Zou Pengfei, Li Kaiqing, Li Ying, Shen Yingjia, Zhang Ziping, Wang Yilei
Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen 361021, China.
College of the Environment and Ecology, Xiamen University, Xiamen 361102, China.
Antibiotics (Basel). 2021 Oct 1;10(10):1199. doi: 10.3390/antibiotics10101199.
Receptor-interacting protein 3 (RIP3) has been demonstrated to be a key regulator not only in cell death pathways including apoptosis and necroptosis but also in inflammation and host immune responses. In this study, a ortholog named is identified in large yellow croaker (). The open reading frame (ORF) of is 1524 bp long and encodes a protein of 507 amino acids (aa). The deduced -RIP3 protein has an N-terminal kinase domain and a C-terminal RHIM domain, and the genome organization of is conserved in teleosts with 12 exons and 11 introns but is different from that in mammals, which comprises 10 exons and 9 introns. Confocal microscopy revealed that -RIP3 is a cytosolic protein. The expression analysis at the mRNA level indicated that is ubiquitously distributed in various tissues/organs, and could be up-regulated under poly I:C, LPS, PGN, and stimulation in vivo. Notably, -RIP3 could induce NF-κB but not IRF3 activation. In addition, -RIP3 co-expression with -TRIF, -MAVS, or -IRF3 significantly abolishes the activation of NF-κB but enhances the induction of IRF3 activity. Moreover, NF-κB activity could be up-regulated when -RIP3 is co-expressed with -RIP1 or -IRF7. These results collectively indicate that -RIP3 acts as an important regulator in host innate immune signaling in teleosts.
受体相互作用蛋白3（RIP3）已被证明不仅是细胞死亡途径（包括凋亡和坏死性凋亡）中的关键调节因子，也是炎症和宿主免疫反应中的关键调节因子。在本研究中，在大黄鱼中鉴定出一个名为的直系同源物。的开放阅读框（ORF）长1524 bp，编码一个507个氨基酸（aa）的蛋白质。推导的-RIP3蛋白具有一个N端激酶结构域和一个C端RHIM结构域，的基因组结构在硬骨鱼中是保守的，有12个外显子和11个内含子，但与哺乳动物不同，哺乳动物包含10个外显子和9个内含子。共聚焦显微镜显示-RIP3是一种胞质蛋白。mRNA水平的表达分析表明，在各种组织/器官中普遍分布，并且在体内聚肌胞苷酸、脂多糖、肽聚糖和刺激下可上调。值得注意的是，-RIP3可诱导NF-κB激活，但不能诱导IRF3激活。此外，-RIP3与-TRIF、-MAVS或-IRF3共表达可显著消除NF-κB的激活，但增强IRF3活性的诱导。此外，当-RIP3与-RIP1或-IRF7共表达时，NF-κB活性可上调。这些结果共同表明，-RIP3在硬骨鱼宿主先天免疫信号传导中起重要调节作用。
