Mdm2 binds p73 alpha without targeting degradation.
The function of the p53 tumor suppressor protein is regulated by interaction with Mdm2, which targets p53 for ubiquitin dependent degradation. We show here that like p53, p73 alpha forms an interaction with Mdm2, both in vitro and in cells, but this does not result in the degradation of the p73 alpha protein. The human papillomavirus E6 protein also fails to degrade p73 alpha, suggesting that the mechanisms governing p73 alpha stability are distinct from those known to regulate p53 stability. However, the interaction of Mdm2 with 73 alpha is sufficient to impede p73 alpha transcriptional function, despite the lack of degradation.
Bálint
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ABL Basic Research Program, NCI-FCRDC, Frederick, Maryland, 21702-1202, USA.
Bates
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Vousden
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D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000502:physiology; D012516:Osteosarcoma; D027383:Papillomaviridae; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex