Stromal cell derived factor-2 (Sdf2): A novel protein expressed in mouse
Stromal cell derived factor-2 (Sdf2): A novel protein expressed in mouse
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DOI：
10.1016/j.biocel.2014.05.024
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Bevilacqua, Estela
中科院分区：
文献类型：
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作者：
Lorenzon-Ojea, Aline R.;Caldeira, Waldir;Bevilacqua, Estela
基质衍生因子（SDFs）家族包括一组由基质细胞产生的分子。SDF1和SDF4是趋化因子；SDF2和SDF5尚未在功能和结构上定义。在人和小鼠中，Sdfl有一个同源基因Sdf2l1，其蛋白质序列相似度为78%，相同度为68%。人SDF2L1是内质网应激诱导基因。在拟南芥中，Sdf2样基因（39%和37%的氨基酸序列与小家鼠Sdf2和Sdf2l1相同）也参与了er胁迫下UPR的激活。我们克隆、表达和纯化了重组Sdf2，并提出了抗Sdf2抗体。我们证明该蛋白在多种组织中表达，并定位于内质网。Sdf2最初被预测为分泌蛋白，因为它在c端缺乏典型的内质网保留信号，我们认为Sdf2可能通过辅助结合蛋白或其他氨基酸序列基序进入内质网，就像同源蛋白Sdf2样一样。此外，来自拟南芥的SDF2-like晶体结构是典型的含有三个MIR基序的β -三叶草；所有被认为对维持β -三叶草桶底层很重要的疏水残基似乎在Sdf2家族中都是保守的。对SDF2家族的43个序列和SDF2L1家族的38个序列进行多重比对也发现了非常相似的残基保守特征。将其氨基酸序列和预测的3D结构与其他Sdf2样蛋白进行比较，我们认为小鼠Sdf2在未折叠蛋白响应和er应激中的作用类似于人类和小鼠的Sdf2l1和拟南芥的Sdf2样蛋白。慢性内质网应激与包括癌症和糖尿病在内的许多人类疾病有关。识别与内质网应激途径相关的新因素有助于识别和定义这种反应的关键靶点。(C) 2014 Elsevier Ltd.版权所有。
The stromal derived factor (SDFs) family comprises a group of molecules generated by stromal cells. SDF1 and SDF4 are chemokines; SDF2 and SDF5 are not yet functionally and structurally defined. In human and mouse, Sdfl has a paralogous gene, Sdf2l1, whose protein sequences are 78% similar and 68% identical. Human SDF2L1 is an endoplasmic reticulum-stress inducible-gene. In Arabidopsis thaliana, SDF2-like (39% and 37% amino acid sequence identity with Mus musculus Sdf2 and Sdf2l1) has also been implicated in activating the UPR in ER-stress. Here we have cloned, expressed and purified recombinant Sdf2 and raised an anti-Sdf2 antibody. We demonstrated that the protein is expressed in several tissues and is localized in the endoplasmic reticulum. We suggest that Sdf2, initially predicted as a secretory protein because it lacks the canonical ER retention signals in its C-terminal, could be ER-resident through accessory binding proteins or other amino acid sequence motifs, as suggested for the homolog protein SDF2-like. Furthermore, the crystal structure of SDF2-like from Arabidopsis thaliana is a typical beta-trefoil containing three MIR motifs; all hydrophobic residues considered important for maintaining the bottom layer of the beta-trefoil barrel seem to be conserved in the Sdf2 family. Multiple alignment using 43 sequences for SDF2 and 38 for SDF2L1 paralogous families also revealed a very similar residue conservation profile. Comparing the amino acid sequence and predicted 3D structure with other Sdf2-like proteins we suggest a role of mouse Sdf2 in the Unfolded Protein Response and ER-stress, similar to that of Sdf2l1 from human and mouse and SDF2-like from Arabidopsis thaliana. Chronic ER stress has been associated with many human diseases including cancer and diabetes. Identification of new factors associated with the ER stress pathway can help to identify and define key targets of this response. (C) 2014 Elsevier Ltd. All rights reserved.