The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation.
A cellular phosphoprotein with an apparent molecular mass of 90 kd (p90) that forms a complex with both mutant and wild-type p53 protein has been characterized, purified, and identified. The protein was identified as a product of the murine double minute 2 gene (mdm-2). The mdm-2 gene enhances the tumorigenic potential of cells when it is overexpressed and encodes a putative transcription factor. To determine if mdm-2 could modulate p53 transactivation, a p53-responsive element from the muscle creatine kinase gene was employed. A wild-type p53-expressing plasmid enhanced the expression of the p53-responsive element when cotransfected into cells that contain no endogenous p53. When a cosmid expressing mdm-2 was transfected with this p53-expressing plasmid, the transactivation of the p53-responsive element was inhibited. Thus, a product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mdm-2 oncogene can inhibit p53-mediated transactivation.
Momand
J
J
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544-1014.
Zambetti
G P
GP
Olson
D C
DC
George
D
D
Levine
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010957:Plasmids; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2