Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin

Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin
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DOI:
10.1073/pnas.94.22.12041
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发表时间:
1997-10-28
影响因子:
11.1
通讯作者:
Kieff, E
Kieff, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Devergne, O;Birkenbach, M;Kieff, E

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EB病毒诱导基因3(Epstein-Barr virus-induced gene 3,EBI 3)是一种与白细胞介素12(interleukin 12,IL-12)的p40亚基相关的新的可溶性促红细胞生成素组分,当EBI 3在细胞中表达时,它在内质网中积累并与分子伴侣钙连接蛋白(calnexin)结合,表明随后的加工和分泌可能依赖于与第二亚基的结合,来自用EBI 3和/或IL-12的p35亚基的表达载体转染的细胞的裂解物和培养基的免疫共沉淀现在揭示了EBI 3与p35的特异性结合。EBB和p35的共表达相互促进它们的分泌。最重要的是,人足月正常胎盘的滋养层成分提取物中的大部分p35与EBIS特异性共免疫沉淀,表明EBI 3在体内与p35形成异源二聚体。由于EBI 3在EBV转化的B淋巴细胞、扁桃体、脾脏和胎盘滋养层中表达,因此EBI 3/p35异源二聚体可能是一种重要的免疫调节剂。
The Epstein-Barr virus-induced gene 3 (EBI3) is a novel soluble hematopoietin component related to the p40 subunit of interleukin 12 (IL-12), When EBI3 was expressed in cells, it accumulated in the endoplasmic reticulum and associated with the molecular chaperone calnexin, indicating that subsequent processing and secretion might be dependent on association with a second subunit, Coimmunoprecipitations from lysates and culture media of cells transfected with expression vectors for EBI3 and/or the p35 subunit of IL-12 now reveal a specific association of EBI3 with p35, Coexpression of EBB and p35 mutually facilitates their secretion, Most importantly, a large fraction of p35 in extracts of the trophoblast component of a human full-term normal placenta specifically coimmunoprecipitated with EBIS, indicating that EBI3 is in a heterodimer with p35, in vivo. Because EBI3 is expressed in EBV-transformed B lymphocytes, tonsil, spleen, and placental trophoblasts, the EBI3/p35 heterodimer is likely to be an important immunomodulator.