We recently revealed a novel mechanism by which p19ARF can induce cell death. We found that the p19ARF mRNA encodes an additional shorter isoform from the same open reading frame, named smARF. smARF is a short lived protein, which is rapidly degraded by the proteasome, but accumulates after inappropriate proliferative signals generated by oncogenes. Surprisingly, smARF translocates to the mitochondria, impairs the structure of the mitochondria and dissipates the mitochondrial membrane potential in a p53 and Bcl-2 family independent manner, ultimately inducing type II caspase-independent autophagic cell death. Addendum to:A Short Mitochondrial form of p19(ARF) Induces Autophagy and Caspase-Independent Cell DeathS. Reef, E. Zalckvar, O. Shifman, S. Bialik, H. Sabanay, M. Oren and A. KimchiMol Cell 2006; 22:463-75
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Reef et al. (2006) studied this question.