Figure 5.

The Notch1 gene is a novel target of p53 at least in normal keratinocytes. Upon DNA damage, p53 transactivates the Notch1 gene so as to induce differentiation. This could be a barrier function against genotoxic stress. In cervical cancer, E6 can down‐regulate expression of Notch1 through inactivation of p53. As Notch1 could function as a tumor suppressor not only in skin but also in cervical keratinocytes, its down‐regulation by E6 might contribute to the development of cervical cancer. In other squamous cell carcinomas, mutation of p53 may have the same consequence. Modified from the authors’ latest publication.^{( 25 )}