Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis

• DOI: 10.1038/s41419-018-1283-5
• Publication Date: 2019-01-22T15:32:17Z
• Authors: Joseph A. Ross; Keiran Vanden Dungen; Kamiko R. Bressler; Mikayla Fredriksen; Divya Khandige Sh...; Nirujah Balasingam; Nehal Thakor
• Keywords: XIAP; Eukaryotic initiation factor; Eukaryotic translation; EIF4E

Abstract Physiological stress conditions attenuate global mRNA translation via modifications of key eukaryotic initiation factors. However, non-canonical mechanisms allow cap-independent certain mRNAs. We have previously demonstrated that eIF5B promotes the encoding antiapoptotic factor, XIAP, during cellular stress. Here, we show depletion sensitizes glioblastoma multiforme cells to TRAIL-induced apoptosis by a pathway involving caspases-8, −9, and −7, with no significant effect on cell cycle progression. evasion promoting several IRES-containing mRNAs, proteins Bcl-xL, cIAP1, c-FLIP S . also nuclear factor erythroid 2-related 2 suggest reactive oxygen species contribute increased under depletion. Finally, leads decreased activation canonical NF-κB pathway. Taken together, our data represents regulatory node, allowing cancer evade pro-survival from