Abstract
The Mdm2 gene is overexpressed in several human tumors. The oncogenic potential of Mdm2 is partially explained by the inhibition of the activity of the tumor suppressor protein p53. Determination of the three-dimensional structure of complexes between Mdm2 and the N-terminal p53 peptide provided a molecular basis for the inhibition of the transcriptional function of p53 by Mdm2. More dramatically, p53 is targeted by Mdm2 for rapid degradation. The Mdm2 gene itself is activated by p53, which gives the opportunity for feed-back control of p53 activity. Keeping p53 under control is most likely the major task of Mdm2 during early development. Recently, evidence was provided for an alternative, p53-independent function of Mdm2.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Gene Expression Regulation, Neoplastic / drug effects
-
Humans
-
Molecular Sequence Data
-
Neoplasm Proteins / chemistry
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / physiology*
-
Nuclear Proteins*
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / physiology*
-
Proto-Oncogene Proteins c-mdm2
-
Structure-Activity Relationship
-
Tumor Suppressor Protein p53 / chemistry
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / physiology*
Substances
-
Neoplasm Proteins
-
Nuclear Proteins
-
Proto-Oncogene Proteins
-
Tumor Suppressor Protein p53
-
MDM2 protein, human
-
Proto-Oncogene Proteins c-mdm2