Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK.
Comp Biochem Physiol B Biochem Mol Biol. 2010 Dec;157(4):364-73. doi: 10.1016/j.cbpb.2010.08.004. Epub 2010 Aug 20.
E3 ubiquitin ligases are central for the selection of proteins targeted for degradation by the ubiquitin proteasome pathway. In this study atrogin-1 (Fbox-32), a major E3 ligase in muscle, has been characterized in Atlantic salmon (Salmo salar). The protein sequence is highly conserved between teleosts and mammals and is characterized by the presence of five conserved motifs related to the identification of protein targets. The genomic structure is conserved between teleosts and mammals and contains 9 exon and 8 introns. The phylogenetic relationship between atrogin-1 and two other closely related ubiquitin E3 ligases FBXO25 and MuRF1 showed atrogin-1 and FBXO25 grouped together with MuRF1 being more distant. The mRNAs were expressed in multiple tissues, atrogin-1 and MuRF1 were most abundant in white muscle and heart whereas FBXO25 had greatest expression in brain, white muscle and heart. The transcriptional modulation of these E3 ligases was examined in starved fish and fish following different immune stimulations. Expression of atrogin-1 and MuRF1 was increased following food deprivation, implementing these two genes in degradation of muscle protein during starvation. During viral infection atrogin-1 expression was not altered, whereas it was increased following stimulation with LPS, indicating an onset of catabolic processes during inflammatory responses.
E3 泛素连接酶是蛋白质被泛素蛋白酶体途径降解的关键。在这项对大西洋三文鱼(Salmo salar)的研究中,对肌肉中的主要 E3 连接酶 atrogin-1(Fbox-32)进行了研究。该蛋白序列在硬骨鱼和哺乳动物之间高度保守,具有五个与蛋白靶标识别相关的保守基序。其基因结构在硬骨鱼和哺乳动物之间是保守的,包含 9 个外显子和 8 个内含子。atrogin-1 与另外两个密切相关的泛素 E3 连接酶 FBXO25 和 MuRF1 的系统进化关系表明,atrogin-1 和 FBXO25 与 MuRF1 聚类在一起,后者与前者的亲缘关系更远。在多种组织中均有这些 mRNAs 的表达,atrogin-1 和 MuRF1 在白肌和心脏中表达最多,而 FBXO25 在大脑、白肌和心脏中的表达最多。在饥饿的鱼和接受不同免疫刺激的鱼中,研究了这些 E3 连接酶的转录调节。在饥饿状态下,由于这两种基因参与了肌肉蛋白的降解,因此 atrogin-1 和 MuRF1 的表达增加。在病毒感染时,atrogin-1 的表达没有改变,而在用 LPS 刺激后,其表达增加,表明在炎症反应期间发生了分解代谢过程。