The Mechanism of CIRP in Regulation of STAT 3 Phosphorylation and Bag‐1/S Expression Upon UVB Radiation

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.