Regulation of Myc function by ARF: checkpoint for Myc-induced oncogenesis.
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 p19(ARF). Human p14(ARF) provides functions similar to p19(ARF). However, p14(ARF) has limited sequence homology with p19(ARF) 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.
Sarkar
Devanand
D
Departments of Pathology, Urology and Neurosurgery, Herbert Irving Comprehensive Caner Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York, USA.
Fisher
Paul B
PB
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D025803:Tumor Suppressor Protein p14ARF