CDK4 and cancer: Milligan et al (1998) reported that p16 acts specifically via its binding to cdk4 to produce G2 delay responses following UVC irradiation in melanoma cell lines. Moreover, p16 is found not only in the nucleus but also in the cytoplasm, especially in cancer cells (Sano et al, 1998; Chen et al, 1999), and plays an important role in the regulation of vascular endothelial growth factor (VEGF) expression and cell senescence (Harada et al, 1999).