Hes1: a new transcription factor that regulates cell survival decisions during ER stress
Through our work in metabolism and ER stress, we have uncovered a transcriptional repressor, Hes1, whose expression is a key determinant of whether cells survive ER stress. Cells facing “irremediable” ER stress commit to apoptosis, through a network of complicated overlapping pathways. We have found that Hes1 is important in this decision- it is upregulated by the UPR and reducing its expression results in increased apoptosis in response to ER stress. Its effects are primarily mediated through repression of Gadd34, a key factor in stress-induced cell death. Gadd34 dephosphorylates the translation initiation factor eIF2 a (which is phosphorylated by the UPR and leads to the attenuation of translation). By repressing Gadd34 expression, Hes1 prevents premature resumption of protein synthesis. We published this work in 2018, and are now examining the effects of this Hes1/Gadd34/eIF2a signaling pathway on cellular quiescence and differentiation, situations where Hes1 plays an important role.
Related Publications
1. Lee JE, Morrison W, Hollien J. Hairy and enhancer of split 1 (HES1) protects
cells from endoplasmic reticulum stress-induced apoptosis through repression of
GADD34. The Journal of biological chemistry. 2018;
293(16):5947-5955. PubMed [journal] PMID: 29491143, PMCID: PMC5912459