[Alternative protein p19ARF: a genuine tumor suppressor gene]

The p16INK4a gene located in the MTS1 (multiple tumor suppressor 1) locus encodes two proteins, p16INK4a and p19ARF, which are structurally unrelated but functionally similar as both inhibit cell cycle progression. In this review, we report and comment new data obtained from mice knockouted for p19ARF without interfering with the expression of p16INK4a. This results in the rapid occurrence of a spectrum of tumors. These data establish that p19ARF is a genuine tumor suppressor protein and raise the questions of the relationship between the two proteins and their respective importance in malignancies.