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).

Simple item page
dc.contributor.authorBressler, Kamiko R.
dc.contributor.authorRoss, Joseph A.
dc.contributor.authorIlnytskyy, Slava
dc.contributor.authorVanden Dungen, Keiran
dc.contributor.authorTaylor, Katrina
dc.contributor.authorPatel, Kush
dc.contributor.authorZovoilis, Athanasios
dc.contributor.authorKovalchuk, Igor
dc.contributor.authorThakor, Nehal
dc.date.accessioned2020-11-05T19:14:33Z
dc.date.available2020-11-05T19:14:33Z
dc.date.issued2021
dc.descriptionAccepted author manuscript.en_US
dc.description.abstractDuring 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.description.peer-reviewYesen_US
dc.identifier.citationBressler, K. R., Ross, J. A., Ilnytskyy, S., Vanden Dungen, K., Taylor, K., Patel, K., Zovoilis, A., Kovalchuk, I., & Thakor, N (2021). 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, 26, 253-264. https://doi.org/10.1007/s12192-020-01174-1en_US
dc.identifier.urihttps://hdl.handle.net/10133/5801
dc.language.isoen_USen_US
dc.publisherSpringeren_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttps://doi.org/10.1007/s12192-020-01174-1en_US
dc.subjectEukaryotic initiation factor 5B (eIF5B)en_US
dc.subjectER stressen_US
dc.subjectTranscriptomeen_US
dc.subjectISRen_US
dc.subjectATF4en_US
dc.subjectJNKen_US
dc.titleDepletion 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.typeArticleen_US
Files
Original bundle
Now showing 1 - 5 of 5
Thumbnail Image
Name:
Kovalchuk-depletion-of-eukaryotic.pdf
Size:
2.63 MB
Format:
Adobe Portable Document Format
Description:
Download
Thumbnail Image
Name:
Supplemental-Table-1.xls
Size:
6.8 MB
Format:
Microsoft Excel
Description:
Download
Thumbnail Image
Name:
Supplemental-Table-2.xls
Size:
7.08 MB
Format:
Microsoft Excel
Description:
Download
Thumbnail Image
Name:
Supplemental-Table-3.xls
Size:
7.06 MB
Format:
Microsoft Excel
Description:
Download
Thumbnail Image
Name:
Kovalchuk-depletion-of-eukaryoticVR.pdf
Size:
7.65 MB
Format:
Adobe Portable Document Format
Description:
REQUEST a copy of the final published version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.75 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Thakor, Nehalkumar
Kovalchuk, Igor