Ubiquitin-dependent degradation of p73 is inhibited by PML Journal Article
| Authors: | Bernassola, F.; Salomoni, P.; Oberst, A.; Di Como, C. J.; Pagano, M.; Melino, G.; Pandolfi, P. P. |
| Article Title: | Ubiquitin-dependent degradation of p73 is inhibited by PML |
| Abstract: | p73 has been identified recently as a structural and functional homologue of the tumor suppressor p53. Here, we report that p73 stability is directly regulated by the ubiquitin-proteasome pathway. Furthermore, we show that the promyelocytic leukemia (PML) protein modulates p73 half-life by inhibiting its degradation in a PML-nuclear body (NB)-dependent manner. p38 mitogen-activated protein kinase-mediated phosphorylation of p73 is required for p73 recruitment into the PML-NB and subsequent PML-dependent p73 stabilization. We find that p300-mediated acetylation of p73 protects it against ubiquitinylation and that PML regulates p73 stability by positively modulating its acetylation levels. As a result, PML potentiates p73 transcriptional and proapoptotic activities that are markedly impaired in Pml-/- primary cells. Our findings demonstrate that PML plays a crucial role in modulating p73 function, thus providing further insights on the molecular network for tumor suppression. |
| Keywords: | human cell; dna-binding proteins; nonhuman; ubiquitin; animal cell; cells, cultured; reverse transcription polymerase chain reaction; apoptosis; proteasome; gene expression; mitogen activated protein kinase p38; neoplasm proteins; small interfering rna; genetic transcription; cancer cell culture; transcription factors; nuclear proteins; enzyme phosphorylation; nucleotide sequence; tumor suppressor proteins; transcription; trans-activators; mitogen-activated protein kinases; fluorescence activated cell sorting; genes, tumor suppressor; complementary dna; acetylation; immunofluorescence microscopy; promyelocytic leukemia protein; retinoic acid receptor; protein p73; cycloheximide; receptors, retinoic acid; p38 mitogen-activated protein kinases; cell nucleus inclusion body; nuclear body; humans; human; priority journal; article; ubiquitinylation |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 199 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2004-06-07 |
| Start Page: | 1545 |
| End Page: | 1557 |
| Language: | English |
| DOI: | 10.1084/jem.20031943 |
| PROVIDER: | scopus |
| PMCID: | PMC2211783 |
| PUBMED: | 15184504 |
| DOI/URL: | |
| Notes: | J. Exp. Med. -- Cited By (since 1996):77 -- Export Date: 16 June 2014 -- CODEN: JEMEA -- Source: Scopus |
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