UVA irradiation-induced activation of activator protein-1 is correlated with induced expression of AP-1 family members in the human keratinocyte cell line HaCaT.

To determine whether the transcription factor activator protein-1 (AP-1) could be modulated by ultraviolet A (UVA) exposure, we examined AP-1 DNA-binding activity and transactivation after exposure to UVA in the human immortalized keratinocyte cell line HaCaT. Maximal AP-1 transactivation was observed with 250 kJ/m2 UVA between 3 and 4 h after irradiation. DNA binding of AP-1 to the target 12-O-tetradecanoylphorbol-13-acetate response element sequence was maximally induced 1-3 h after irradiation. Both de novo transcription and translation contributed to the UVA-induced AP-1 DNA binding. c-Fos was implicated as a primary component of the AP-1 DNA-binding complex. Other components of the complex included Fra-2, c-Jun, JunB and JunD. UVA irradiation induced protein expression of c-Fos, c-Jun, Fra-1 and Fra-2. Phosphorylated forms of these induced proteins were determined at specific time points. A strong correlation existed between UVA-induced AP-1 activity and accumulation of c-Fos, c-Jun and Fra-1 proteins. UVA irradiation also induced c-fos and c-jun mRNA expression and transcriptional activation of the c-fos gene promoter. These results demonstrate that UVA irradiation activates AP-1 and that c-fos induction may play a critical role in the response of these human keratinocytes to UVA irradiation.