title: Subcellular distribution of p53 and p73 are differentially regulated by MDM2.
abstract: The binding of MDM2 targets p53, but not p73, for degradation, whereas it suppresses the transactivation function of both proteins. MDM2 also mediates p53 nuclear export, but its role in the regulation of p73 distribution is unknown at the present time. We show here that, in sharp contrast to p53, MDM2 induces p73 to form nuclear aggregates that colocalize with MDM2 but are distinct from the promyelocytic leukemia dots. The MDM2 ring-domain that is necessary for mediating p53 nuclear export is not required for the induction of the p73 nuclear aggregates. Using a domain-swapping approach, we demonstrate that the inability of p73 to nuclear-export is attributable to its nonfunctional nuclear-export sequence.
authors.affiliation: Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: L
authors.initials: L
authors.lastname: Nie
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: Z M
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2