Journal
CANCER CELL
Volume 32, Issue 5, Pages 561-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.09.008
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Funding
- National Nature Science Foundation of China [31301131]
- Science and Innovation Commission Foundation of Shenzhen [JCYJ20150901164734162]
- Natural Science Foundation of Heilongjiang Province [C201431]
- Special Foundation for Distinguished Talents of Harbin [2014RFXXJ055]
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Reactive oxygen species (ROS) haveemerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance both in vitro and in vivo. Thus, iASPP is an antioxidative factor and represents a promising target to improve cancer treatment, regardless of p53 status.
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