Dugan Jae W, Albor Amador, David Larry, Fowlkes Jonathan, Blackledge Marc T, Martin Tammy M, Planck Stephen R, Rosenzweig Holly L, Rosenbaum James T, Davey Michael P
Department of Veterans Affairs Medical Center, Portland, OR 97239-2999, USA.
Mol Immunol. 2009 Dec;47(2-3):560-6. doi: 10.1016/j.molimm.2009.09.025. Epub 2009 Oct 23.
Nucleotide-binding and oligomerization domain-2 (NOD2) is an intracellular protein involved in innate immunity and linked to chronic inflammatory diseases in humans. Further characterization of the full spectrum of proteins capable of binding to NOD2 may provide new insights into its normal functioning as well as the mechanisms by which mutated forms cause disease. Using a proteomics approach to study human THP-1 cells, we have identified 2'-5'-oligoadenylate synthetase type 2 (OAS2), a dsRNA binding protein involved in the pathway that activates RNase-L, as a new binding partner for NOD2. The interaction was confirmed using over-expression of OAS2 and NOD2 in HEK cells. Further confirmation was obtained by detecting NOD2 in immunoprecipitates of endogenous OAS2 in THP-1 cells. Finally, over-expression of NOD2 in THP-1 cells led to enhanced RNase-L activity in cells treated with poly(I:C), a mimic of double-stranded RNA virus infection. These data indicate connectivity in pathways involved in innate immunity to bacteria and viruses and suggest a regulatory role whereby NOD2 enhances the function of RNase-L.
核苷酸结合寡聚化结构域2（NOD2）是一种参与固有免疫的细胞内蛋白，与人类慢性炎症性疾病相关。对能够与NOD2结合的蛋白质全谱进行进一步表征，可能会为其正常功能以及突变形式导致疾病的机制提供新的见解。通过蛋白质组学方法研究人类THP-1细胞，我们鉴定出2'-5'-寡腺苷酸合成酶2型（OAS2），一种参与激活RNase-L途径的双链RNA结合蛋白，作为NOD2的新结合伴侣。使用OAS2和NOD2在HEK细胞中的过表达证实了这种相互作用。通过检测THP-1细胞内源性OAS2免疫沉淀中的NOD2获得了进一步的证实。最后，THP-1细胞中NOD2的过表达导致在用聚肌胞苷酸（poly(I:C)，双链RNA病毒感染的模拟物）处理的细胞中RNase-L活性增强。这些数据表明了参与细菌和病毒固有免疫的途径之间的联系，并提示NOD2具有增强RNase-L功能的调节作用。
