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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3686-3690. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-09-3782.
NEOPLASIA The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damageFrom the Cancer Biology and Genetics Program, Department of Pathology, Sloan-Kettering Institute, Weill Graduate School of Medical Sciences, Cornell University, New York, NY.
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
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| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
-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. 
