Verónica A Bahamondes Lorca1, Bernardo D Bastidas Mayorga2, Lingying Tong3, Shiyong Wu4. 1. Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA; Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 2. Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. 3. Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. Electronic address: tongl1@ohio.edu. 4. Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. Electronic address: wus1@ohio.edu.
Abstract
AIM: To elucidate the mechanism behind the sustained high levels of phosphorylated eIF2α in HaCaT cells post-UVB. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Novel mechanism to explain the prolonged phosphorylation of eIF2α post-UVB irradiation.
AIM: To elucidate the mechanism behind the sustained high levels of phosphorylated eIF2α in HaCaT cells post-UVB. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Novel mechanism to explain the prolonged phosphorylation of eIF2α post-UVB irradiation.
Authors: Mufti R Farrukh; Ul A Nissar; Quadri Afnan; Rather A Rafiq; Love Sharma; Shajrul Amin; Peerzada Kaiser; Parduman R Sharma; Sheikh A Tasduq Journal: J Dermatol Sci Date: 2014-04-13 Impact factor: 4.563
Authors: Verónica A Bahamondes Lorca; Mary Kate McCulloch; Óscar Ávalos-Ovando; Alexander O Govorov; Faiz Rahman; Shiyong Wu Journal: Photochem Photobiol Date: 2022-01-05 Impact factor: 3.521