An essential function of the extreme C-terminus of MDM2 can be provided by MDMX.
MDM2 (HDM2) is a ubiquitin ligase that can target the p53 tumor suppressor protein for degradation. The RING domain is essential for the E3 activity of MDM2, and we show here that the extreme C-terminal tail of MDM2 is also critical for efficient E3 activity. Loss of E3 function in ... MDM2 mutants deleted of the C-terminal tail correlated with a failure of these mutants to oligomerize with MDM2, or with the related protein MDMX (HDMX). However, MDM2 containing point mutations within the C-terminus that inactivated E3 function retained the ability to oligomerize with the wild-type MDM2 RING domain and MDMX, and our results indicate that oligomers containing both wild-type MDM2 and a C-terminal mutant protein retain E3 function both in auto-degradation and degradation of p53. Interestingly, the E3 activity of C-terminal point mutants of MDM2 can also be supported by interaction with wild-type MDMX, suggesting that MDMX can directly contribute to E3 function.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Line, Tumor, Humans, Molecular Sequence Data, Mutagenesis, Mutation, Nuclear Proteins, Point Mutation, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transfection, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases
Amino Acid Sequence, Animals, Cell Line, Tumor, Humans, Molecular Sequence Data, Mutagenesis, Mutation, Nuclear Proteins, Point Mutation, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transfection, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases
EMBO J.
Date: Jan. 10, 2007
PubMed ID: 17159902
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