A smARF way to die: a novel short isoform of p19ARF is linked to autophagic cell death.
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.
Reef
Sharon
S
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Kimchi
Adi
A
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D020033:Protein Isoforms