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Research Paper
p14ARF Directly Interacts with Myc Through the Myc BoxII Domain
Stefano Amente, Barbara Gargano, Francesca Varrone, Luca Ruggiero, David Dominguez-Sola, Luigi Lania and Barbara Majello
volume 5 | issue 3
march 2006Pages: 287-291
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Myc is a well known proto-oncogene encoding for a transcription factor whose activity is tightly regulated in the cellular context. Myc was the first oncogene recognized to activate the ARF tumor suppressor gene which suppresses cell proliferation partly through stabilization of the p53 tumor suppressor protein but which also has p53-independent growth-suppressive functions. Recent studies have indicated that mouse p19ARF negatively regulates Myc’s transcriptional activity. We here show that the human p14ARF directly associates with Myc and relocates Myc from the nucleoplasm to the nucleolus. We found that p14ARF interacts with the Myc-Max complex and the binding of p14ARF does not interfere with Myc-Max interaction in vitro. Protein interaction assays define the Myc BoxII as a critical domain required for interaction with p14ARF. Moreover, we identify 30 amino acids encompassing Myc BoxII domain required for p14ARF interaction and co-localization in vivo. Finally, we show that p14ARF down regulates Myc activated transcription and that this activity cannot be addressed to an intrinsic p14ARF repressor domain.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.