SuPr-1-mediated desumoylation regulates the repressor activity of ΔNp63α

ΔNp63α is exclusively expressed in stem cells and progenitor cells of the stratified epithelia. It promotes cell proliferation by antagonizing p53 and related TAp63/TAp73. Here, we report that specific desumoylation by SUMO protease SuPr-1 provides a fine-tuning mechanism for ΔNp63α repressor activity. We found that disrupting the sumoylation site compromised ΔNp63α repressor activity profoundly against TAp63γ and TAp73β-mediated transcription activation, but not to p53-mediated transcription. We further found that SuPr-1 specifically bound to sumoylated ΔNp63α and hydrolyzed SUMO. Consequently, SuPr-1 expression reduced ΔNp63α repressor activity to TAp63γ and TAp73β, whereas p53-mediated transactivation was unaffected. Collectively, these data suggest that SuPr-1-mediated ΔNp63α desumoylation elaborately regulates epithelial growth.