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.

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment

“…There is no evidence in data bases to support an alternatively translated form of eIF4A1 and therefore the most likely explanation is that in these cells eIF4A1 contains a protein modification (Figure 2aii), which could be sumolyation, as described. 40 However, the precise type of modification has yet to be identified. Ribosomal protein expression was also examined and the data again confirmed the array data, with significant decreases in expression of ribosomal proteins, including RPS23, RPL7A, RPL9 and RPL15 (Figure 2bi, bii and c).…”

SUMOylation of Rb enhances its binding with CDK2 and phosphorylation at early G1 phase

“… 32 Furthermore, the loss of the SUMO pathway significantly inhibited cell proliferation, whereas the growth of cells overexpressing SUMO2 was markedly promoted. 33,34 Additionally, the global SUMOylation is elevated in patient-derived tumor tissues compared with normal tissues. 35 Consistent with these findings, we have observed increased global SUMOylation during cell cycle progress in the S/M phase ( Fig.…”