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The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage.

Articolo
Data di Pubblicazione:
2005
Abstract:
The promyelocytic leukemia (PML) gene, a tumor suppressor inactivated in acute promyelocytic leukemia (APL), regulates apoptosis induced by DNA damage. However, the molecular mechanisms by which PML modulates apoptosis following genotoxic stress are only partially elucidated. PML is essential for p53-dependent induction of programmed cell death upon gamma-irradiation through PML-nuclear body (NB)-mediated control of p53 acetylation. Here, we show that PML selectively regulates proapoptotic transcription factors upon different types of DNA damage. We find that Pml inactivation protects fibroblasts from UV-induced apoptosis in a p53-independent manner. We demonstrate that c-Jun is required for UV-induced apoptosis and that PML is essential for both c-Jun transcriptional activation and DNA binding upon UV radiation. We find that PML physically interacts with c-Jun and that upon UV radiation the PML-NBs reorganize into novel nuclear microspeckled structures (UV-NBs), where PML and c-Jun dynamically accumulate. These data identify a novel PML-dependent pathway for c-Jun transcriptional activation and induction of apoptosis in response to DNA damage and shed new light on the role of PML in tumor suppression.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
Animals; Apoptosis; Cells; Cultured; DNA Damage; Embryo; Mammalian; Mice; Knockout; Neoplasm Proteins; Nuclear Proteins; Protein Binding; Proto-Oncogene Proteins c-jun; Transcription Factors; Transcriptional Activation; Transfection; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Ultraviolet Rays
Elenco autori:
P. Salomoni;R. Bernardi;S. Bergmann;A. Changou;S. Tuttle;P. P. Pandolfi
Autori di Ateneo:
PANDOLFI DE RINALDIS Pier Paolo
Link alla scheda completa:
https://iris.unito.it/handle/2318/61495
Pubblicato in:
BLOOD
Journal
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Dati Generali

URL

http://dx.doi.org/10.1182/blood-2004-09-3782
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