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. 2018 May 25;9(40):26130–26143. doi: 10.18632/oncotarget.25452

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Copyright: © 2018 Chai et al.

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

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HSP90 inhibitors have a dual function for wild-type p53, inhibiting MDM2/MDM4-mediated ubiquitination to augment the expression and stimulating proteasome-mediated degradation to decrease the expression. Overproduction of p53 can further up-regulate the degradation. The inhibitors also facilitate proteasome-mediated degradation of mutated p53 but the effect on MDM2/MDM4-mediated ubiquitination of mutated p53 was unclear.