p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state.

摘要: Although much is known about the underlying mechanisms of p53 activity and regulation, factors that influence diversity duration responses are not well understood. Here we describe a unique mode regulation involving alternative splicing TP53 gene. We found use an 3′ splice site in intron 6 generates isoform, dubbed p53Ψ. At molecular level, p53Ψ unable to bind DNA does transactivate canonical target genes. However, like certain gain-of-function mutants, attenuates expression E-cadherin, induces markers epithelial-mesenchymal transition, enhances motility invasive capacity cells through mechanism cyclophilin D activity, component mitochondrial inner pore permeability. Hence, propose encodes separation-of-function isoform that, although lacking tumor suppressor/transcriptional activities, able induce prometastatic program transcriptionally independent manner.