IDH1, a CHOP and C/EBPβ-responsive gene under ER stress, sensitizes human melanoma cells to hypoxia-induced apoptosis

• IDH1 was up-regulated in melanoma cells under ER stress.
• CHOP and C/EBPβ transcriptionally regulated IDH1 under ER stress.
• Elevated IDH1 sensitized human melanoma cells to hypoxia-induced apoptosis and promoted HIF-1α degradation.
• CHOP and C/EBPβ affected tunicamycin and hypoxia induced apoptosis through up-regulating IDH1.

Isocitrate dehydrogenase1 (IDH1) is of great importance in cell metabolism and energy conversion. However, alterations in IDH1 in response to stress and excise-regulated mechanisms are not well described. Here we investigated gene expression profiles under ER stress in melanoma cells and found that IDH1 was dramatically increased with ER stress induced by tunicamycin. Elevated IDH1 subsequently sensitized human melanoma cells to hypoxia-induced apoptosis and promoted HIF-1α degradation. In addition, we revealed that CHOP and C/EBPβ were involved in hypoxia-induced apoptosis via transcriptional regulation of IDH1 expression. Our data indicate that IDH1, regulated by CHOP and C/EBPβ in response to ER stress treatment, inhibits survival of melanoma cells under hypoxia and promotes HIF-1α degradation. Therefore, we propose that IDH1 may serve as a valuable target for melanoma therapy.