UVB-induced eIF2α phosphorylation in keratinocytes depends on decreased ATF4, GADD34 and CReP expression levels

• DOI: 10.1016/j.lfs.2021.120044
• Publication Date: 2021-10-11T14:58:46Z
• Authors: Verónica A. Baham...; Bernardo D. Basti...; Lingying Tong; Shiyong Wu
• Keywords: Keratinocytes; 0303 health sciences; Ultraviolet Rays; Eukaryotic Initiation Factor-2; Gene Expression; Protein Serine-Threonine Kinases; Activating Transcription Factor 4; Cell Line; eIF-2 Kinase; 03 medical and health sciences; Gene Expression Regulation; Protein Biosynthesis; Protein Phosphatase 1; Endoribonucleases; Humans; Phosphorylation; Transcription Factor CHOP; Signal Transduction

To elucidate the mechanism behind the sustained high levels of phosphorylated eIF2α in HaCaT cells post-UVB.In this study, expression levels of the machinery involved in the dephosphorylation of eIF2α (GADD34, CReP and PP1), as well as the PERK-eIF2α-ATF4-CHOP, IRE1α/XBP1s and ATF6α signaling cascades, were analyzed by western blot and fluorescence microscope.Our data showed that UVB induces the phosphorylation of eIF2α, which induces the translation of ATF4 and consequently the expression of CHOP and GADD34. Nevertheless, UVB also suppresses the translation of ATF4 and GADD34 in HaCaT cells via a p-eIF2α independent mechanism. Therefore, the lack of ATF4, GADD34 and CReP is responsible for the sustained phosphorylation of eIF2α. Finally, our data also showed that UVB selectively modifies PERK and downregulates ATF6α expression but does not induce activation of the IRE1α/XBP1s pathway in HaCaT cells.Novel mechanism to explain the prolonged phosphorylation of eIF2α post-UVB irradiation.