Tumor suppressor p63 regulates Pirh2 ubiquitin ligase expression

Abstract

Tumor suppressor protein p63 is a transcription factor of the p53 protein family. It is known that the proteins of this family, namely, p53, p63, and p73, perform a number of common tumor suppressor functions related to cell cycle regulation, apoptosis, and malignant transformation of cells, in addition to specific functions in the development of tissues and organs. All the proteins of the p53 family are regulated at post-translational level due to ubiquitination by E3 ligases and subsequent proteasomal degradation. The expression of the majority of E3 ubiquitin ligases, which modify the proteins of the p53 family, is regulated by the same proteins, thus forming negative feedback with them. In the present study, we first showed that the expression of the PIRH2 (RCHY1) gene, the product of which ubiquitinates all three members of the p53 family, is also regulated by p63. Regulation of the PIRH2 expression occurs at the transcription level by only fulllength TAp63 isoform, but not ΔNp63 isoform, which lacks a transactivation domain.