Mdm2: keeping p53 under control

• Published in: Oncogene Vol. 15; no. 9; pp. 1001 - 1010
• Main Authors: PIETTE, J, NEEL, H, MARECHAL, V
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 28.08.1997; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Amino Acid Sequence; Animals; Biochemistry, Molecular Biology; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Life Sciences; MDM2 protein; Molecular and cellular biology; Molecular Sequence Data; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Nuclear Proteins; p53 Protein; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-mdm2; Structure-Activity Relationship; Transcription; Tumor suppressor genes; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - physiology; Tumors; Binding protein; Vertebrata; Regulation(control); Cell function; Mammalia; Domain structure; Molecular structure; Feedback regulation; Molecular interaction; Review; Gene expression; Tumor suppressor gene; Amino Acid Sequence Animals Gene Expression Regulation; Neoplastic/drug effects Humans Molecular Sequence Data Neoplasm Proteins/chemistry/genetics/physiology Nuclear Proteins Proto-Oncogene Proteins/chemistry/genetics/physiology Proto-Oncogene Proteins c-mdm2 Structure-Activity Relationship Tumor Suppressor Protein p53/chemistry/genetics/physiology
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1201432

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.