Li Yan-Wei, Wang Zheng, Mo Ze-Quan, Li Xia, Luo Xiao-Chun, Dan Xue-Ming, Li An-Xing
State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, PR China.
College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, PR China.
Fish Shellfish Immunol. 2015 Jan;42(1):153-8. doi: 10.1016/j.fsi.2014.10.041. Epub 2014 Nov 8.
Myeloid differentiation factor 88 (MyD88) and Toll-interacting protein (Tollip) are two important regulatory proteins of the Toll-like receptor (TLR) signaling pathways. In this paper, a Tollip sequence of grouper (Epinephelus coioides) was identified and the signal transduction functions of Tollip and MyD88 were studied. The full length of E. coioides Tollip (EcTollip) cDNA with an open reading frame (ORF) of 1734 nucleotides encoded a putative protein of 274 amino acid residues. The EcTollip protein had conservative domains with mammalian homologous proteins, and high identity (78%-95%) with other vertebrates. MyD88 and Tollip were distributed in the HeLa cytoplasm in a highly condensed form. Over-expression of MyD88 could activate nuclear factor-κB (NF-κB) and its function was dependent on the death domain and ID domain on the N-terminal. Some important functional sites of mammalian MyD88 also affected fish MyD88 signal transduction. Tollip impaired NF-κB signals activated by MyD88, and its activity was dependent on the coupling of ubiquitin to the endoplasmic reticulum degradation (CUE) domain on the C-terminal. These results suggest that MyD88 and Tollip of fish and mammals are conservative on function during evolution.
髓样分化因子88（MyD88）和Toll相互作用蛋白（Tollip）是Toll样受体（TLR）信号通路的两个重要调节蛋白。本文鉴定了石斑鱼（Epinephelus coioides）的Tollip序列，并研究了Tollip和MyD88的信号转导功能。石斑鱼Tollip（EcTollip）cDNA全长1734个核苷酸，开放阅读框（ORF）编码一个由274个氨基酸残基组成的假定蛋白。EcTollip蛋白与哺乳动物同源蛋白具有保守结构域，与其他脊椎动物具有高度同源性（78%-95%）。MyD88和Tollip以高度浓缩的形式分布在HeLa细胞质中。MyD88的过表达可激活核因子κB（NF-κB），其功能依赖于N端的死亡结构域和ID结构域。哺乳动物MyD88的一些重要功能位点也影响鱼类MyD88的信号转导。Tollip损害MyD88激活的NF-κB信号，其活性依赖于泛素与C端内质网降解（CUE）结构域的偶联。这些结果表明，鱼类和哺乳动物的MyD88和Tollip在进化过程中的功能是保守的。
