title: SUMO-2 promotes mRNA translation by enhancing interaction between eIF4E and eIF4G.
abstract: 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.
authors: 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.
authors: Li-zhao
authors: LZ
authors: Chen
authors: 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.
authors: Xiang-yun
authors: XY
authors: Li
authors: First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Hong
authors: H
authors: Huang
authors: First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Wei
authors: W
authors: Xing
authors: First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Wei
authors: W
authors: Guo
authors: Cell-based Biotherapy Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Jing
authors: J
authors: He
authors: Cell-based Biotherapy Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Zhi-ya
authors: ZY
authors: Sun
authors: Cell-based Biotherapy Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: An-xiong
authors: AX
authors: Luo
authors: First department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Hua-ping
authors: HP
authors: Liang
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Jing
authors: J
authors: Hu
authors: 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.
authors: Zheng-guo
authors: ZG
authors: Wang
authors: Department of Dermatology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou Zhejiang, China.
authors: Yun-sheng
authors: YS
authors: Xu
authors: Fourth department, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Xiang
authors: X
authors: Xu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D045325:HCT116 Cells; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012315:RNA Caps; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C517852:4EGI-1 compound; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D006835:Hydrazones; D046912:Multiprotein Complexes; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D012333:RNA, Messenger; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D013844:Thiazoles; D019938:Cyclin D1