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The ARF/Oncogene Pathway Activates p53 Acetylation within the DNA Binding Domain
Hestia Mellert, Stephen M. Sykes, Maureen E. Murphy and Steven B. McMahon
volume 6 | issue 11
1 June 2007Pages: 1304 - 1306
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Stabilization of the p53 tumor suppressor is a critical event in the response to various forms of cellular stress. Two distinct signaling pathways are thought to lead to this stabilization, depending on the type of cellular stress encountered. Genotoxic stress, such as chromosomal breaks or lesions induced by chemotherapeutic agents, result in the activation of the well-characterized DNA damage response pathway. Conversely, cellular stress that results from the aberrant activation of oncogenes triggers p53 stabilization via the induction of the p19ARF pathway. While activation of the DNA damage pathway ultimately causes a complex array of post-translational modifications on p53, activation few if any modifications have been demonstrated to occur following activation of the p19ARF pathway. We and others have recently identified a novel modification on p53, acetylation of lysine 120 within the DNA binding domain. This acetylation event is eliminated by tumor-derived mutations in p53 and its presence is required for the tumor suppressor apoptotic function of p53. We demonstrate here that both the DNA damage response pathway and the p19ARF/oncogene stress pathway induce the acetylation of p53 at lysine 120.
Authors
Hestia Mellert
University of Pennsylvania, Philadelphia, Pennsylvania
Stephen M. Sykes
University of Pennsylvania, Philadelphia, Pennsylvania
Maureen E. Murphy
Fox Chase Cancer Center, Philadelphia, Pennsylvania
Steven B. McMahon
Kimmel Cancer Center; Philadelphia, PA
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 PDF If 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.