The DNp63a protein interacts with Y-box binding protein 1 and promotes its ubiquitination

The p63 protein is a member of p53 transcription factor family. The TP63 gene encodes isoforms that contain (TA) or lack (DN) a transactivation domain. The p63 protein plays an essential role for the development of skin and other epidermal derivatives. The ΔNp63α isoform is mainly expressed in the basal layer of the squamous epithelia and is restricted to progenitor cells with proliferative potential. We demonstrate that ΔNp63α can physically and functionally interact with the Y-box-binding protein 1 (YB-1).YB-1 belongs to the cold-shock domain protein superfamily and performs a wide variety of cellular functions, including transcriptional and translational regulation of proteins involved in the proliferation, survival and cellular differentiation. Inasmuch, as the level of YB-1 drastically increases in tumor cells, this protein is considered to be one of the most indicative markers of malignant tumors. The YB-1 C-terminal region contains a number of distinct sites that can be targeted for post-translational modifications such as phosphorylation, acetylation and ubiquitination. We have observed that expression of ΔNp63α, but not ΔNp63γ, causes accumulation of YB-1 high molecular weight forms in the nuclear compartment and we provide evidence that these are ubiquitinated YB-1 forms. The functional role of YB-1 ubiquitination by ΔNp63α is currently under investigation.