ONCOPROTEIN MDM2 IS A UBIQUITIN LIGASE E3 FOR TUMOR-SUPPRESSOR P53

The tumor suppressor p53 is degraded by the ubiquitin-proteasome syste m. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MD M2 oncoprotein, A ubiquitin molecule bound MDM2 through sulfhydroxy bo nd which is characteristic of ubiquitin ligase (E3)-ubiquitin binding, The cysteine residue in the carboxyl terminus of MDM2 was essential f or the activity, These data suggest that the MDM2 protein, which is in duced by p53, functions as a ubiquitin ligase, E3, in human papillomav irus-uninfected cells which do not have E6 protein, (C) 1997 Federatio n of European Biochemical Societies.