Small mitochondrial ARF (smARF) is located in both the nucleus and cytoplasm, induces cell death, and activates p53 in mouse fibroblasts.
The ARF transcript produces two proteins, the full-length ARF, p19(ARF), and a short mitochondrial version, smARF. To explore the functional difference between the two, we generated GFP-fused expression vectors for each protein and introduced them into NIH3T3 murine fibroblasts, which sustains a global deletion in the INK4a locus but contains a functional p53 gene. GFP-p19ARF was located within the nucleolus as previously reported, whereas GFP-smARF was detected mainly in the nucleoplasm. GFP-smARF induced cell death although to a slightly lesser extent than p19ARF. GFP-smARF stabilized p53 thereby inducing expression of the target genes, MDM2 and p21. We suggest that smARF has functions other than mitochondria-mediated autophagy, and induces p53 expression and cell death via a novel mechanism.
Ueda
Yuko
Y
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
Koya
Terutsugu
T
Yoneda-Kato
Noriko
N
Kato
Jun-Ya
JY
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins