Activating transcription factor 4 plays a major role in shaping the transcriptional response to isoginkgetin in HCT116 cells.

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.

Cyclin-dependent kinase inhibitor 1 plays a more prominent role than activating transcription factor 4 or the p53 tumour suppressor in thapsigargin-induced G1 arrest.

Background: Thapsigargin (Tg) is a compound that inhibits the SERCA calcium transporter leading to decreased endoplasmic reticulum (ER) Ca2+ levels. Many ER chaperones are required for proper folding of membrane-associated and secreted proteins, and they are Ca2+ dependent. Therefore, Tg leads to the accumulation of misfolded proteins in the ER, activating the unfolded protein response (UPR) to help restore homeostasis.

Microarray dataset supporting a role for ATF4 in isoginkgetin-induced gene expression in HCT116 cells.

Isoginkgetin (IGG) is a compound originally derived from the leaves of trees. It was subsequently identified through a chemical screen to be an inhibitor of both the major and minor spliceosome, with an IC50 value of 30 µM [1]. Little is currently known about the overall effects of spliceosome inhibition on human cells.

Isoginkgetin leads to decreased protein synthesis and activates an ATF4-dependent transcriptional response.

Isoginkgetin (IGG) is a small molecule inhibitor of pre-mRNA splicing. Failure to accurately remove introns could lead to the production of aberrant mRNAs and proteins. The cellular responses to splicing stress are not well defined.