Activating transcription factor 4 plays a major role in shaping the transcriptional response to isoginkgetin in HCT116 cells.
ATF4
Endoplasmic reticulum stress
Integrated stress response
Isoginkgetin
Thapsigargin
Unfolded protein response
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Oct 2024
02 Oct 2024
Historique:
received:
25
03
2024
accepted:
25
09
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
2
10
2024
Statut:
epublish
Résumé
Activating transcription factor 4 (ATF4) plays a central role in the integrated stress response (ISR) and one overlapping branch of the unfolded protein response (UPR). We recently reported that the splicing inhibitor isoginkgetin (IGG) induced ATF4 protein along with several known ATF4-regulated transcripts in a response that resembled the ISR and UPR. However, the contribution of ATF4-dependent and -independent transcriptional responses to IGG exposure was not known. Here we used RNA-sequencing in HCT116 colon cancer cells and an isogenic subline lacking ATF4 to investigate the contribution of ATF4 to IGG-induced changes in gene expression. Approximately 85% of the IGG-responsive DEGs in HCT116 cells were also differentially expressed in response to the ER stressor thapsigargin (Tg) and these were enriched for genes associated with the UPR and ISR. Most of these were positively regulated by IGG with impaired responses in the ATF4-deficient cells. Nonetheless, there were DEGs that responded similarly in both cell lines. The ATF4-independent IGG-induced DEGs included several metal responsive transcripts encoding metallothionines and a zinc transporter. Taken together, the predominant IGG response was ATF4-dependent in these cells and resembled the UPR and ISR while a second less prominent response involved the ATF4-independent regulation of metal responsive mRNAs.
Identifiants
pubmed: 39358540
doi: 10.1038/s41598-024-74391-8
pii: 10.1038/s41598-024-74391-8
doi:
Substances chimiques
Activating Transcription Factor 4
145891-90-3
isoginkgetin
0
Biflavonoids
0
ATF4 protein, human
0
Thapsigargin
67526-95-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22938Subventions
Organisme : Canada Research Chairs Program
ID : CRC-2020-00060
Organisme : Canadian Foundation of Innovation John Evan's Leadership Fund
ID : 233109
Organisme : Ontario Research Fund
ID : 40569
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : RGPIN-2021-02806
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : RGPIN-2019-06146
Informations de copyright
© 2024. The Author(s).
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