The INK4a/ARF locus in murine tumorigenesis

The INK4a/ARF locus is regarded as one of the most important anti-tumoral defenses that mammalian organisms possess. The characterization of its two gene products, p16(INK4a) and p19(ARF), has provided a great insight on the functioning of the tumor suppressors Rb and p53, respectively. Present evidence indicates that the INK4a/ARF locus is transcriptionally activated by oncogenic stresses, resulting in cell-cycle arrest or apoptosis. Here, I review the evidence accumulated on the involvement of the INK4a/ARF locus in murine tumorigenesis. Also, I summarize the phenotype of the different transgenic mouse models based on the inactivation of the INK4a/ARF locus.