Chen Li-zhao, Li Xiang-yun, Huang Hong, Xing Wei, Guo Wei, He Jing, Sun Zhi-ya, Luo An-xiong, Liang Hua-ping, Hu Jing, Wang Zheng-guo, Xu Yun-sheng, Xu Xiang
First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China; Department of Neurosurgery, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China; Cell-based Biotherapy Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
PLoS One. 2014 Jun 27;9(6):e100457. doi: 10.1371/journal.pone.0100457. eCollection 2014.
Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process.
小泛素样修饰物（SUMO）蛋白通过与靶蛋白进行可逆的共价结合来调节许多重要的真核细胞过程。除了其许多众所周知的生物学效应，如蛋白质的亚细胞易位、亚核结构形成以及转录活性的调节外，我们在此表明SUMO-2在mRNA翻译中也发挥作用。SUMO-2通过增强真核起始因子4E（eIF4E）与真核起始因子4G（eIF4G）之间的相互作用，促进了活性真核起始因子4F（eIF4F）复合物的形成，并诱导了一部分蛋白质的翻译，如细胞周期蛋白D1和c-myc，这些蛋白质对细胞增殖和凋亡至关重要。正如预期的那样，SUMO-2的过表达可以部分抵消4EGI-1（一种eIF4E/eIF4G相互作用的小分子抑制剂）对eIF4F复合物形成、帽依赖性蛋白翻译、细胞增殖和凋亡的破坏作用。另一方面，通过短发夹RNA（shRNA）敲低SUMO-2会部分损害帽依赖性翻译和细胞增殖，并促进细胞凋亡。这些结果共同表明SUMO-2的结合在蛋白质合成中起着关键的调节作用。因此，本报告可能有助于对哺乳动物蛋白质翻译的基本理解，并为SUMO在此过程中的作用提供一些新的线索。
Zotero 插件