p19ras brings a new twist to the regulation of p73 by Mdm2.
p53 is the most commonly mutated gene in human cancer. It is now known that the p53 family proteins p63 and p73 play important roles in tumor suppression as well as in development. Because p63 and p73 are rarely mutated in human cancer, understanding the signaling pathways that activate p63 and p73 will not only shed light on the developmental processes regulated by p63 and p73 but may also yield insight into ways to harness p63 and p73 activity for cancer therapy. Recent research has shown that an alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta through a mechanism that involves the E3 ubiquitin ligase Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63.
Harms
Kelly Lynn
KL
Department of Cell Biology, University of Alabama, Birmingham, AL 35294, USA.
Chen
Xinbin
X
D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D011905:Genes, ras; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017354:Point Mutation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D016283:Proto-Oncogene Proteins p21(ras)