IκB Kinase β Promotes Cell Survival by Antagonizing p53 Functions through ΔNp73α Phosphorylation and Stabilization

摘要: ΔNp73α, a dominant-negative inhibitor of p53 and p73, exhibits antiapoptotic transforming activity in vitro models is often found to be upregulated human cancers. The mechanisms involved the regulation ΔNp73α protein levels normal cancer cells are poorly characterized. Here, we show that IκB kinase beta (IKKβ) increases stability independently its ability activate NF-κB. IKKβ associates with phosphorylates at serine 422 (S422), leading accumulation nucleus, where it binds represses several p53-regulated genes. S422A mutation abolished IKKβ-mediated stabilization inhibition gene expression. Inhibition by chemical inhibitors, overexpression mutants, or silencing siRNA also resulted destabilization, which under these conditions was rapidly translocated into cytoplasm degraded calpain-mediated mechanism. We present evidence for cross talk cancer-derived cell lines primary Our data unveil new mechanism p73 network.