Activation of the transcription factor Oct-1 in response to DNA damage

Mammalian cells exhibit complex cellular responses to genotoxic stress, inc luding cell cycle checkpoint, DNA repair, and apoptosis. Inactivation of th ese important biological events will result in genomic instability and cell transformation. It has been demonstrated that gene activation is a critica l initial step during the cellular response to DNA damage. A number of inve stigations have shown that transcription factors are involved in the regula tion of stress-inducible genes. These transcription Factors include p53, c- Myc, and AP-1 (c-fos and c-jun). However, the role for the octamer-binding transcription factor Oct-1 in the DNA damage-activated response is unknown. In this report, we have presented the novel observation that the transcrip tion factor Oct-1 is induced after cells are exposed to multiple DNA-damagi ng agents and therapeutic agents, including UV radiation, methylmethane sul fonate, ionizing radiation, etoposide, cisplatin, and camptothecin, The ind uction of the Oct-1 protein is mediated through a posttranscriptional mecha nism and does not require the normal cellular function of the tumor suppres sor p53, indicating that the Oct-1 protein, as a transcription factor, may play a role in p53-independent gene activation. In addition to increased pr otein level, the activity of Oct-1 DNA binding to its specific consensus se quence is also enhanced by DNA damage. Therefore, these results have implic ated that the transcription factor Oct-1 might participate in cellular resp onse to DNA damage, particularly in p53-independent gene activation.