The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage Journal Article
| Authors: | Salomoni, P.; Bernardi, R.; Bergmann, S.; Changou, A.; Tuttle, S.; Pandolfi, P. P. |
| Article Title: | The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage |
| 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 γ-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. © 2005 by The American Society of Hematology. |
| Keywords: | controlled study; nonhuman; ultraviolet radiation; animal cell; mouse; animals; mice; mice, knockout; dna damage; cells, cultured; apoptosis; embryo; transcription initiation; neoplasm proteins; protein binding; transcription factor; transfection; protein p53; transcription factors; nuclear proteins; cancer inhibition; tumor suppressor gene; tumor suppressor proteins; promyelocytic leukemia; fibroblast; tumor suppressor protein p53; gamma irradiation; gene control; gene inactivation; dna binding; ultraviolet rays; genotoxicity; promyelocytic leukemia protein; trans-activation (genetics); protein c jun; pml gene; proto-oncogene proteins c-jun |
| Journal Title: | Blood |
| Volume: | 105 |
| Issue: | 9 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2005-05-01 |
| Start Page: | 3686 |
| End Page: | 3690 |
| Language: | English |
| DOI: | 10.1182/blood-2004-09-3782 |
| PUBMED: | 15626733 |
| PROVIDER: | scopus |
| PMCID: | PMC1895009 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 28" - "Export Date: 24 October 2012" - "CODEN: BLOOA" - "Source: Scopus" |
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