NAD(P)H Quinone Oxidoreductase Protects TAp63γ from Proteasomal Degradation and Regulates TAp63γ-Dependent Growth Arrest

摘要

Backgroundp63 is a member of the p53 transcription factor family. p63 is expressed from two promoters resulting in proteins with opposite functions: the transcriptionally active TAp63 and the dominant-negative ΔNp63. Similar to p53, the TAp63 isoforms induce cell cycle arrest and apoptosis. The ΔNp63 isoforms are dominant-negative variants opposing the activities of p53, TAp63 and TAp73. To avoid unnecessary cell death accompanied by proper response to stress, the expression of the p53 family members must be tightly regulated. NAD(P)H quinone oxidoreductase (NQO1) has recently been shown to interact with and inhibit the degradation of p53. Due to the structural similarities between p53 and p63, we were interested in studying the ability of wild-type and polymorphic, inactive NQO1 to interact with and stabilize p63. We focused on TAp63γ, as it is the most potent transcription activator and it is expected to have a role in tumor suppression.