Hdmx and Mdm2 can repress transcription activation by p53 but not by p63.
The p53 protein is involved in cell cycle arrest and apoptosis. To ensure that cells under non-stressed conditions are able to grow, p53 sets up a negative feedback loop by inducing Mdm2. Mdm2 is able to both inhibit the transcriptional regulation by p53 and to degrade it, thus maintaining p53 inactive until it is required. The Mdm2 related protein, Hdmx, has also been shown to inhibit the transcriptional activation of p53 but is unable to degrade it. A few years ago, the p53 family member, p63 was identified. Like p53, p63 is able to induce p53 target genes and it was shown to be able to cause cell cycle arrest and apoptosis. In this study we report that, despite the similarities between p53 and p63, neither Hdmx nor Mdm2 are able to interact with p63, to repress p63-induced transcription or to affect its half-life.
Little
N A
NA
Department of Molecular and Cell Biology, Leiden University Medical Centre, PO Box 9503, 2300 RA Leiden, The Netherlands.
Jochemsen
A G
AG
D017209:Apoptosis; D001859:Bone Neoplasms / Q000473:pathology; D002453:Cell Cycle; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins; D005246:Feedback; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006207:Half-Life; D006801:Humans; D008565:Membrane Proteins; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins; D012516:Osteosarcoma / Q000473:pathology; D010750:Phosphoproteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000502:physiology; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex