title: SuPr-1-mediated desumoylation regulates the repressor activity of DeltaNp63alpha.
abstract: DeltaNp63alpha 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 DeltaNp63alpha repressor activity. We found that disrupting the sumoylation site compromised DeltaNp63alpha repressor activity profoundly against TAp63gamma and TAp73beta-mediated transcription activation, but not to p53-mediated transcription. We further found that SuPr-1 specifically bound to sumoylated DeltaNp63alpha and hydrolyzed SUMO. Consequently, SuPr-1 expression reduced DeltaNp63alpha repressor activity to TAp63gamma and TAp73beta, whereas p53-mediated transactivation was unaffected. Collectively, these data suggest that SuPr-1-mediated DeltaNp63alpha desumoylation elaborately regulates epithelial growth.
authors.affiliation: Department of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Gwanak-Ku, Seoul, Republic of Korea.
authors.forename: Hae-Ock
authors.initials: HO
authors.lastname: Lee
authors.forename: Mioh
authors.initials: M
authors.lastname: Cho
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyo-Sil
authors.initials: HS
authors.lastname: Kim
authors.forename: Yungdae
authors.initials: Y
authors.lastname: Yun
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D010447:Peptide Hydrolases; D008239:Lysine