TY - JOUR
T1 - Does Nrf2 contribute to p53-mediated control of cell survival and death?
AU - Chen, Weimin
AU - Jiang, Tao
AU - Wang, Huihui
AU - Tao, Shasha
AU - Lau, Alexandria
AU - Fang, Deyu
AU - Zhang, Donna D.
PY - 2012/12/15
Y1 - 2012/12/15
N2 - In response to oxidative stress, the transcription factor Nrf2 is upregulated and controls activation of many genes that work in concert to defend cells from damages and to maintain cellular redox homeostasis. p53 has been regarded as the guardian of the genome through its pro-oxidant and antioxidant functions. Under low levels of reactive oxygen species (ROS), "normal" amounts of p53 upregulates expression of antioxidant genes, protecting macromolecules from ROS-induced damage. However, at high levels or extended exposure of ROS, p53 expression is enhanced, activating pro-oxidant genes and resulting in p53-dependent apoptosis. We observed a two-phase Nrf2 expression controlled by p53. (i) The induction phase: when p53 expression is relatively low, p53 enhances the protein level of Nrf2 and its target genes to promote cell survival in a p21-dependent manner. (ii) The repression phase: when p53 expression is high, the Nrf2-mediated survival response is inhibited by p53. Our observation leads to the hypothesis that the p53-mediated biphasic regulation of Nrf2 may be key for the tumor-suppressor function of p53 by coordinating cell survival and death pathways.
AB - In response to oxidative stress, the transcription factor Nrf2 is upregulated and controls activation of many genes that work in concert to defend cells from damages and to maintain cellular redox homeostasis. p53 has been regarded as the guardian of the genome through its pro-oxidant and antioxidant functions. Under low levels of reactive oxygen species (ROS), "normal" amounts of p53 upregulates expression of antioxidant genes, protecting macromolecules from ROS-induced damage. However, at high levels or extended exposure of ROS, p53 expression is enhanced, activating pro-oxidant genes and resulting in p53-dependent apoptosis. We observed a two-phase Nrf2 expression controlled by p53. (i) The induction phase: when p53 expression is relatively low, p53 enhances the protein level of Nrf2 and its target genes to promote cell survival in a p21-dependent manner. (ii) The repression phase: when p53 expression is high, the Nrf2-mediated survival response is inhibited by p53. Our observation leads to the hypothesis that the p53-mediated biphasic regulation of Nrf2 may be key for the tumor-suppressor function of p53 by coordinating cell survival and death pathways.
UR - http://www.scopus.com/inward/record.url?scp=84867694835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867694835&partnerID=8YFLogxK
U2 - 10.1089/ars.2012.4674
DO - 10.1089/ars.2012.4674
M3 - Review article
C2 - 22559194
AN - SCOPUS:84867694835
SN - 1523-0864
VL - 17
SP - 1670
EP - 1675
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 12
ER -