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The Mechanism of CIRP in Regulation of STAT 3 Phosphorylation and Bag‐1/S Expression Upon UVB Radiation
Author(s) -
Sun Weichao,
Liao Yi,
Yi Qian,
Wu Shiyong,
Tang Liling,
Tong Lingying
Publication year - 2018
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12981
Subject(s) - hacat , phosphorylation , stat , microbiology and biotechnology , jak stat signaling pathway , signal transduction , chemistry , kinase , stat3 , biology , in vitro , biochemistry , receptor tyrosine kinase
Abstract Cold‐inducible RNA binding protein ( CIRP ) is a stress‐inducible protein, which could be activated by various cellular stresses, such as hypothermia, hypoxia and UV irradiation. Our previous study indicated that UVB radiation (3 mJ cm −2 ) induces CIRP expression, which promotes keratinocytes growth, survival and eventually transformation via activation of STAT 3‐Bag‐1/S signaling cascade. However, the mechanism(s) of CIRP in regulating p‐ STAT 3 activation and Bag‐1/S expression have not been fully elucidated. In this study, we demonstrate that repeated exposure of UVB radiation (3 mJ cm −2 ) or overexpression of CIRP could lead to an elevation of the phosphorylation of Janus kinase ( JAK ) family proteins ( JAK 2 and JAK 3) in HaCaT cells. The increased phosphorylation of the JAK s correlates to an increased phosphorylation of STAT 3 (p‐ STAT 3) in the cells; inhibiting JAK s using JAK inhibitor I lead to a reduction of STAT 3 phosphorylation and Bag‐1/S expression in wild type HaCaT and CIRP stably transfected HaCaT cells with or without UVB exposure. Furthermore, our data indicated that inhibiting the downstream factor of CIRP , NF ‐ κ B, using BAY 11‐7085 could also decrease the p‐ STAT 3. These results lead us to propose that CIRP mediates the activation of STAT 3‐Bag‐1/S signaling cascade via activating the JAK s and NF ‐ κ B signaling pathways.