Abstract 3910: Acetylation of ΔNp63α by Tip60 affects its stability

Abstract

Abstract p63, a member of the transcription factor p53 family, exists as six different isoforms due to the usage of alternative promoter sites and splicing. ΔNp63α is the most abundant and predominant isoform and is identified to being involved in epithelial morphogenesis. ΔNp63α expression is up-regulated in non-melanoma skin cancers. We have identified ΔNp63α as a potential target for acetylation by the Tat Interacting Protein 60 kDa (TIP60) histone acetyltransferase (HAT) by mass spectometry. Co-expression of ΔNp63α with Tip60 leads to stabilization of ΔNp63α protein levels. The change in protein levels are not due to an increase in transcription or translation, and is likely the result of stabilization by post-translational modification as confirmed by half-life studies in presence of cycloheximide and measurement of transcript levels by quantitative reverse transcriptase PCR. This was further supported by our observations that ΔNp63α and Tip60 interact using immunoprecipitation studies. ΔNp63α levels are not affected by Tip60 HAT mutant, but increased with Tip60 double sumoylation mutant which retains its acetyltransferase ability. These results identify a possible biologically important interaction between ΔNp63α and Tip60, warranting further investigation. Citation Format: Andrew J. Stacy, Zachary J. Smith, Jin Zhang, Madhavi Kadakia. Acetylation of ΔNp63α by Tip60 affects its stability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3910. doi:10.1158/1538-7445.AM2015-3910