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.
Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA.
Life Sci. 2021 Dec 1;286:120044. doi: 10.1016/j.lfs.2021.120044. Epub 2021 Oct 9.
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.
阐明 HaCaT 细胞经 UVB 照射后磷酸化 eIF2α 持续高水平的机制。
在这项研究中，通过 Western blot 和荧光显微镜分析了参与 eIF2α 去磷酸化的机制（GADD34、CReP 和 PP1）以及 PERK-eIF2α-ATF4-CHOP、IRE1α/XBP1s 和 ATF6α 信号级联的表达水平。
我们的数据表明，UVB 诱导 eIF2α 的磷酸化，从而诱导 ATF4 的翻译，进而导致 CHOP 和 GADD34 的表达。然而，UVB 还通过一种 p-eIF2α 非依赖性机制抑制 HaCaT 细胞中 ATF4 和 GADD34 的翻译。因此，ATF4、GADD34 和 CReP 的缺乏是 eIF2α 持续磷酸化的原因。最后，我们的数据还表明，UVB 选择性修饰 PERK 并下调 ATF6α 的表达，但不会诱导 HaCaT 细胞中 IRE1α/XBP1s 途径的激活。
解释 UVB 照射后 eIF2α 持续磷酸化的新机制。
