1993 | Xiangwei Wu, J. Henri Bayle, David Olson, and Arnold J. Levine
The p53 protein, a transcription factor, can bind to specific DNA sequences and activate the transcription of adjacent genes. The *mdm-2* gene contains a p53 DNA-binding site and a genetically responsive element, allowing its expression to be regulated by wild-type p53 protein levels. The mdm-2 protein, in turn, complexes with p53 and reduces its ability to act as a positive transcription factor at the *mdm-2* gene-responsive element. This creates an autoregulatory feedback loop where p53 regulates *mdm-2* gene transcription, and mdm-2 regulates p53 protein activity. The study demonstrates that wild-type p53 protein stimulates *mdm-2* mRNA and protein levels, and that mdm-2 negatively regulates p53-mediated trans-activation of the *mdm-2* gene. This feedback loop helps maintain a balance between p53 activity and mdm-2 levels, potentially influencing cell proliferation and growth arrest.The p53 protein, a transcription factor, can bind to specific DNA sequences and activate the transcription of adjacent genes. The *mdm-2* gene contains a p53 DNA-binding site and a genetically responsive element, allowing its expression to be regulated by wild-type p53 protein levels. The mdm-2 protein, in turn, complexes with p53 and reduces its ability to act as a positive transcription factor at the *mdm-2* gene-responsive element. This creates an autoregulatory feedback loop where p53 regulates *mdm-2* gene transcription, and mdm-2 regulates p53 protein activity. The study demonstrates that wild-type p53 protein stimulates *mdm-2* mRNA and protein levels, and that mdm-2 negatively regulates p53-mediated trans-activation of the *mdm-2* gene. This feedback loop helps maintain a balance between p53 activity and mdm-2 levels, potentially influencing cell proliferation and growth arrest.