Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W
Institute of Biochemistry, Humboldt-University, Medical Faculty (Charité), Berlin, Germany.
FASEB J. 1998 Apr;12(6):469-78.
A novel protein complex has been identified in human cells that has a molecular mass of approximately 450 kDa. It consists of at least eight different subunits including JAB1, the Jun activation-domain binding protein 1, and Trip15, the thyroid hormone receptor-interacting protein 15. The purified complex contains COP9 and COP11 protein homologs and is very similar, if not identical, to the plant COP9 complex involved in light-mediated signal transduction. The isolated JAB1-containing particle has kinase activity that phosphorylates IkappaBalpha, the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino-terminal activation domain of c-Jun. The phosphorylation of c-Jun requires the carboxy terminus of the protein containing the DNA binding and dimerization domains. Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence similarities to regulatory components of the 26S proteasome, which could indicate the existence of common substrate binding sites. Immunofluorescence staining reveals that the new complex shows a subcellular distribution similar to that of the 26S proteasome. The functional relationship of the two particles in regulating transcriptional activity is discussed. Considering the putative role of the complex in signal transduction and its widespread occurrence, we suggest the name JAB1-containing signalosome.
在人类细胞中已鉴定出一种新型蛋白质复合物，其分子量约为450 kDa。它由至少八个不同的亚基组成，包括JAB1（Jun激活域结合蛋白1）和Trip15（甲状腺激素受体相互作用蛋白15）。纯化的复合物含有COP9和COP11蛋白同源物，并且与参与光介导信号转导的植物COP9复合物非常相似（如果不是完全相同的话）。分离出的含JAB1颗粒具有激酶活性，可磷酸化IkappaBalpha、p105的羧基末端以及c-Jun氨基末端激活域的Ser63和/或Ser73。c-Jun的磷酸化需要该蛋白包含DNA结合和二聚化结构域的羧基末端。新复合物的三个亚基——Sgn3、Sgn5/JAB1和Sgn6——与26S蛋白酶体的调节成分表现出序列相似性，这可能表明存在共同的底物结合位点。免疫荧光染色显示，新复合物的亚细胞分布与26S蛋白酶体相似。讨论了这两种颗粒在调节转录活性方面的功能关系。考虑到该复合物在信号转导中的假定作用及其广泛存在，我们建议将其命名为含JAB1信号体。
