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Starvation promotes REV1 SUMOylation and p53-dependent sensitization of melanoma and breast cancer cells.
+ Author Affiliations
- 1Department of Biological Sciences, Davis School of Gerontology, University of Southern California
- 2Longevity Institute, University of Southern California
- ↵* Corresponding Author:
Valter D Longo, Department of Biological Sciences, Davis School of Gerontology, University of Southern California, 3715 McClintock Ave, Los Angeles, CA, 90089, Italy vlongo@usc.eduAbstractShort-term starvation or fasting can augment cancer treatment efficacy, but can also be effective in delaying cancer progression in the absence of chemotherapy. However, the underlying molecular mechanism remains elusive. REV1, a specialized DNA polymerase involved in DNA repair, has emerged as an essential component in genome maintenance and cancer development. Here we describe REV1 as an important signaling node linking nutrient sensing and metabolic control to cell fate. We show that REV1 is a novel binding partner of the tumor suppressor p53 and regulates its activity, and that short-term starvation facilitates the modifications of these proteins. Under starvation, REV1 is modified by SUMO2/3, resulting in consequent relief of REV1's inhibition of p53 and enhancing p53 activation, pro-apoptotic genes expression and in turn p53-mediated apoptosis in breast cancer and melanoma cells. Thus, fasting, through its effect on REV1, is a promising non-toxic strategy to increase p53-dependent cell death and to enhance the efficacy of cancer therapies.
http://cancerres.aac...N-14-2249.short