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.

Bernassola, F., Salomoni, P., Oberst, A., Di Como, C., Pagano, M., Melino, G., et al. (2004). Ubiquitin-dependent degradation of p73 is inhibited by PML. JOURNAL OF EXPERIMENTAL MEDICINE, 199(11), 1545-1557 [10.1084/jem.20031943].

Ubiquitin-dependent degradation of p73 is inhibited by PML

BERNASSOLA, FRANCESCA;MELINO, GENNARO;
2004-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11
English
Con Impact Factor ISI
Acetylation; Apoptosis; Nuclear body; Transcription; Ubiquitinylation
Bernassola, F., Salomoni, P., Oberst, A., Di Como, C., Pagano, M., Melino, G., et al. (2004). Ubiquitin-dependent degradation of p73 is inhibited by PML. JOURNAL OF EXPERIMENTAL MEDICINE, 199(11), 1545-1557 [10.1084/jem.20031943].
Bernassola, F; Salomoni, P; Oberst, A; Di Como, C; Pagano, M; Melino, G; Pandolfi, Pp
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/29862
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