Nucleolar p19ARF, unlike mitochondrial smARF, is incapable of inducing p53-independent autophagy

Autophagy
Sharon Reef, Adi Kimchi

Abstract

ARF mRNA encodes two distinct proteins, the nucleolar p19(ARF), and a shorter mitochondrial isoform, named smARF. Inappropriate proliferative signals generated by proto-oncogenes, such as c-Myc and E2F1, can elevate both p19(ARF) and smARF proteins. The two ARF isoforms differ not only in their localization but also in their functions. Nucleolar p19(ARF) inhibits cell growth mainly by activating p53 or by inhibiting ribosomal biogenesis. In contrast, mitochondrial smARF can induce dissipation of the mitochondrial membrane potential and autophagy in a p53 independent manner. Recently, it was proposed by Abida et al., that similar to smARF, the nucleolar p19(ARF) can also induce p53 independent autophagy, but in contrast to smARF it does so from within the nucleolus. Our current work shown here indicates, however, that if the ectopic expression of p19(ARF) is restricted to the nucleolus it cannot induce autophagic vesicle formation. Only upon extreme overexpression, when p19(ARF) is localized to extra nuclear compartments, can it trigger p53-independent autophagic vesicle formation. Thus, our experiments indicate that the nucleolar p19(ARF) is incapable of inducing autophagy from within the nucleolus.

Citations

Jun 4, 2013·Seminars in Cancer Biology·Federico PietrocolaGuido Kroemer
Jul 27, 2010·Mechanisms of Ageing and Development·Cristina Mammucari, Rosario Rizzuto
Apr 22, 2015·Cancer Letters·Juanjuan TangJunnian Zheng
Aug 21, 2013·Cell Metabolism·Celia R BerkersKaren H Vousden
Mar 23, 2010·Trends in Cell Biology·Gregor M BalaburskiMaureen E Murphy
Apr 18, 2009·Biochimica Et Biophysica Acta·Eugenia MorselliGuido Kroemer
Mar 28, 2009·Cell Death and Differentiation·A Eisenberg-LernerA Kimchi
Jul 19, 2011·Oncogene·W K K WuJ J Y Sung
Sep 14, 2014·The Journal of Biological Chemistry·Karl GrenierEdward A Fon
Dec 6, 2016·Frontiers in Genetics·Aristides G EliopoulosVassilis G Gorgoulis
Jun 28, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jolieke G van OosterwijkCharles J Sherr

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