SuPr-1-mediated desumoylation regulates the repressor activity of DeltaNp63alpha.
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.
Lee
Hae-Ock
HO
Department of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Gwanak-Ku, Seoul, Republic of Korea.
Cho
Mioh
M
Lee
Jung-Hwa
JH
Kim
Hyo-Sil
HS
Yun
Yungdae
Y
Lee
Hyunsook
H
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*
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