UVB irradiation regulates Cox-2 mRNA stability through AMPK and HuR in human keratinocytes.
Considerable evidence has demonstrated that UVB irradiation is a strong carcinogen for nonmelanoma skin cancer. Up-regulation of cyclooxygenase-2 (Cox-2) has been shown to be a crucial event in human keratinocytes in their responses to UVB irradiation. To further understand the molecular mechanisms governing Cox-2 regulation, we found that UVB irradiation significantly increased Cox-2 mRNA stability by inducing cytoplasmic localization and protein abundance of human antigen R (HuR). We also found that AMP-activated kinase (AMPK) mediates these events and that UVB reduces AMPK activity by down-regulating LKB1 kinase. Finally, we propose a novel model in which UVB regulates Cox-2 mRNA stability through the LKB1/AMPK pathway.
Zhang
Jack
J
Arizona Cancer Center, Tucson, Arizona 85724, USA.
Bowden
G Tim
GT
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D020871:RNA Stability / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection; D014466:Ultraviolet Rays
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D055372:AMP-Activated Protein Kinases