TY - JOUR
T1 - Starvation promotes REV1 SUMOylation and p53-dependent sensitization of melanoma and breast cancer cells
AU - Shim, Hong Seok
AU - Wei, Min
AU - Brandhorst, Sebastian
AU - Longo, Valter D.
N1 - Publisher Copyright:
©2015 AACR.
PY - 2015/3/15
Y1 - 2015/3/15
N2 - Short-term starvation or fasting can augment cancer treatment efficacy and can be effective in delaying cancer progression in the absence of chemotherapy, but the underlying molecular mechanisms of action remain elusive. Here, we describe the role of REV1, a specialized DNA polymerase involved in DNA repair, 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. Under starvation, REV1 is modified by SUMO2/3, resulting in the relief of REV1's inhibition of p53 and enhancing p53's effects on proapoptotic gene expression and apoptosis in breast cancer and melanoma cells. Thus, fasting in part through its effect on REV1 is a promising nontoxic strategy to increase p53-dependent cell death and to enhance the efficacy of cancer therapies.
AB - Short-term starvation or fasting can augment cancer treatment efficacy and can be effective in delaying cancer progression in the absence of chemotherapy, but the underlying molecular mechanisms of action remain elusive. Here, we describe the role of REV1, a specialized DNA polymerase involved in DNA repair, 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. Under starvation, REV1 is modified by SUMO2/3, resulting in the relief of REV1's inhibition of p53 and enhancing p53's effects on proapoptotic gene expression and apoptosis in breast cancer and melanoma cells. Thus, fasting in part through its effect on REV1 is a promising nontoxic strategy to increase p53-dependent cell death and to enhance the efficacy of cancer therapies.
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U2 - 10.1158/0008-5472.CAN-14-2249
DO - 10.1158/0008-5472.CAN-14-2249
M3 - Article
C2 - 25614517
AN - SCOPUS:84941622631
SN - 0008-5472
VL - 75
SP - 1056
EP - 1067
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -