%0 Journal Article
%T C-terminal ¦Á Domain of p63 Binds to p300 to Coactivate ¦Â-Catenin
%A Iyoko Katoh
%A Kohji Moriishi
%A Ryu-Ichiro Hata
%A Shun-ichi Kurata
%A Yojiro Maehata
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2019
%R 10.1016/j.neo.2019.03.010
%X TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is essential for ectodermal tissue development and suppresses malignant progression of carcinomas. The most abundant isoform, ¦¤Np63¦Á (referred to as p63), lacks the N-terminal transactivation (TA) domain, and was originally characterized as a dominant-negative type suppressor against p53 family proteins. It also binds to TCF/LEF to inhibit ¦Â-catenin. Nevertheless, transcriptional activation by p63 has also been observed in varied systems. To understand the puzzling results, we analyzed the structure¨Cfunction relationship of p63 in the control of ¦Â-catenin-dependent transcription. p63 acted as a suppressor of moderately induced ¦Â-catenin. However, when nuclear targeted S33Y ¦Â-catenin was applied to cause the maximum enhancer activation, p63 displayed a ¦Â-catenin-coactivating function. The DNA-binding domain of p63 and the target sequence facilitated it. Importantly, we newly found that, despite the absence of TA domain, p63 was associated with p300, a general adaptor protein and chromatin modifier causing transcriptional activation. C-terminal ¦Á domain of p63 was essential for p300-binding and for the coactivator function. These results were related to endogenous p63-p300 complex formation and Wnt/¦Â-catenin-responsive gene regulation by p63 in squamous cell carcinoma lines. The novel p63-p300 interaction may be involved in positive regulation of gene expression in tissue development and carcinogenesis
%K TA
%K transactivation
%K NF-Y
%K nuclear transcription factor Y
%K WRE
%K Wnt response element
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462804/