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dc.contributor.author Bressler, Kamiko R.
dc.contributor.author Ross, Joseph A.
dc.contributor.author Ilnytskyy, Slava
dc.contributor.author Vanden Dungen, Keiran
dc.contributor.author Taylor, Katrina
dc.contributor.author Patel, Kush
dc.contributor.author Zovoilis, Athanasios
dc.contributor.author Kovalchuk, Igor
dc.contributor.author Thakor, Nehal
dc.date.accessioned 2020-11-05T19:14:33Z
dc.date.available 2020-11-05T19:14:33Z
dc.date.issued 2020
dc.identifier.citation Bressler, K. R., Ross, J. A., Ilnytskyy, S., Vanden Dungen, K., Taylor, K., Patel, K., Zovoilis, A., Kovalchuk, I., & Thakor, N (2020). Depletion of eukaryotic initiation factor 5B (eIF5B) reprograms the cellular transcriptome and leads to activation of endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK). Cell Stress and Chaperones. Advance online publication. https://doi.org/10.1007/s12192-020-01174-1 en_US
dc.identifier.uri https://hdl.handle.net/10133/5801
dc.description Permission to archive accepted author manuscript. Embargo in effect until Oct 29, 2021. en_US
dc.description.abstract During the integrated stress response (ISR), global translation initiation is attenuated; however, noncanonical mechanisms allow for the continued translation of specific transcripts. Eukaryotic initiation factor 5B (eIF5B) has been shown to play a critical role in canonical translation as well as in noncanonical mechanisms involving internal ribosome entry site (IRES) and upstream open reading frame (uORF) elements. The uORF-mediated translation regulation of activating transcription factor 4 (ATF4) mRNA plays a pivotal role in the cellular ISR. Our recent study confirmed that eIF5B depletion removes uORF2-mediated repression of ATF4 translation, which results in the upregulation of growth arrest and DNA damage-inducible protein 34 (GADD34) transcription. Accordingly, we hypothesized that eIF5B depletion may reprogram the transcriptome profile of the cell. Here, we employed genome-wide transcriptional analysis on eIF5B-depleted cells. Further, we validate the up- and downregulation of several transcripts from our RNA-seq data using RT-qPCR. We identified upregulated pathways including cellular response to endoplasmic reticulum (ER) stress, and mucin-type O-glycan biosynthesis, as well as downregulated pathways of transcriptional misregulation in cancer and T cell receptor signaling. We also confirm that depletion of eIF5B leads to activation of the c-Jun N-terminal kinase (JNK) arm of the mitogen-activated protein kinase (MAPK) pathway. This data suggests that depletion of eIF5B reprograms the cellular transcriptome and influences critical cellular processes such as ER stress and ISR. en_US
dc.language.iso en_US en_US
dc.publisher Springer en_US
dc.subject Eukaryotic initiation factor 5B (eIF5B) en_US
dc.subject ER stress en_US
dc.subject Transcriptome en_US
dc.subject ISR en_US
dc.subject ATF4 en_US
dc.subject JNK en_US
dc.title Depletion of eukaryotic initiation factor 5B (eIF5B) reprograms the cellular transcriptome and leads to activation of endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK). en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Chemistry and Biochemistry en_US
dc.publisher.department Department of Biological Sciences en_US
dc.publisher.department Department of Neuroscience en_US
dc.description.peer-review Yes en_US
dc.publisher.institution University of Lethbridge en_US
dc.publisher.institution University of Calgary en_US
dc.publisher.url https://doi.org/10.1007/s12192-020-01174-1 en_US


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