Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53.
The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.
Honda
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School of Life Science, Tokyo University of Pharmacy and Life Science, Japan.
Tanaka
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Yasuda
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D000595:Amino Acid Sequence; D002457:Cell Extracts; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D017421:Sequence Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*
D002457:Cell Extracts; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D008025:Ligases