Regulation of Myc function by ARF: Checkpoint for Myc-induced oncogenesis

Abstract

The alterative reading frame (ARF) protein is unique in its capacity to interact with Mdm2 thus facilitating p53-dependent cell cycle arrest and apoptosis. ARF also acts in a p53-independent manner in which it binds to Myc and interferes with transcriptional activation by Myc thereby inhibiting Myc-induced cell proliferation and transformation. Interestingly, ARF does not interfere with apoptosis induction by Myc. ARF-Myc interaction studies have been performed with mouse p19ARF. Human p14ARF provides functions similar to p19ARF. However, p14ARF has limited sequence homology with p19ARF and these proteins show subtle functional differences, especially in the contexts of immortalization and senescence. The studies by Amente et al. confirm that interaction of p14 ARF with Myc also interferes with the transcriptional activity of Myc thus establishing the general role of ARF as a checkpoint for Myc-induced oncogenesis. ©2006 Landes Bioscience.