Stress-induced c-Jun activation mediated by Polo-like kinase 3 in corneal epithelial cells.
Polo-like kinase 3 (Plk3) activation occurs after exposure to environmental or genotoxic stresses. Plk3 regulates cell fate through regulating cell cycle progression. UV irradiation is one of the major environmental stresses that affect corneal epithelial wound healing. In the present study, we report that UV irradiation activated Plk3 and that Plk3 interacts with AP-1 and c-Jun, which appears to be important to mediate corneal epithelial cell apoptosis after UV irradiation. Recombinant Plk3, as well as Plk3 immunoprecipitated from UV-irradiated cells, phosphorylated c-Jun in vitro. The phosphorylation of c-Jun by Plk3 immunoprecipitates was not altered by the pre-removal of JNK from the cell lysates. In addition, the effect of UV irradiation-induced phosphorylation of c-Jun and apoptosis were not significantly affected by knockdown of JNK mRNA. Co-immunoprecipitation reveals that Plk3 and c-Jun directly interacted with each other. Consistently, Plk3 co-localized with c-Jun to the nucleus after UV irradiation. Further, modulating Plk3 activities by overexpressing Plk3 or its mutants significantly affected UV irradiation-induced c-Jun activity and subsequent apoptosis. Our results thus provide for the first time that Plk3 mediates UV irradiation-induced c-Jun activation by phosphorylating c-Jun, suggesting that Plk3 plays an important role in mediating programmed cell death of corneal epithelial cells after UV irradiation.
Wang
Ling
L
Department of Medicine, Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California Los Angeles, Torrance, California 90502, USA.
Dai
Wei
W
Lu
Luo
L
D017209:Apoptosis; D003315:Cornea / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays; D000097868:Polo-like Kinases