SEARCH:   Advanced

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. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-09-3782v1 105/9/3686    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Salomoni, P. Articles by Pandolfi, P. P. Search for Related Content PubMed PubMed Citation Articles by Salomoni, P. Articles by Pandolfi, P. P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 30, 2004 Accepted December 13, 2004 The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage Paolo Salomoni, Rosa Bernardi, Stephan Bergmann, Austin Changou, Sara Tuttle, and Pier Paolo Pandolfi* Cancer Biology and Genetics Program, Department of Pathology, Sloan-Kettering Institute, Weill Graduate School of Medical Sciences, Cornell University, Memorial Sloan-Kettering Cancer Center, New York, NY, USA * Corresponding author; email: p-pandolfi{at}ski.mskcc.org. 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 -irradiation through PML-Nuclear Body (NB)-mediated control of p53 acetylation. Here we show that PML selectively regulates pro-apoptotic 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. We find that PML physically interacts with c-Jun and that upon UV 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The ProMiscuousLy (PML) exciting nuclear protein has another partner Kirsten Jensen, Carol Shiels, and Paul S. Freemont Blood 2005 105: 3393-3394. [Full Text] [PDF] This article has been cited by other articles: O. Yogev, S. Anzi, K. Inoue, and E. Shaulian Induction of Transcriptionally Active Jun Proteins Regulates Drug-induced Senescence J. Biol. Chem., November 10, 2006; 281(45): 34475 - 34483. [Abstract] [Full Text] [PDF] S. O. Boe, M. Haave, A. Jul-Larsen, A. Grudic, R. Bjerkvig, and P. E. Lonning Promyelocytic leukemia nuclear bodies are predetermined processing sites for damaged DNA J. Cell Sci., August 15, 2006; 119(16): 3284 - 3295. [Abstract] [Full Text] [PDF] C. Bellodi, K. Kindle, F. Bernassola, D. Dinsdale, A. Cossarizza, G. Melino, D. Heery, and P. Salomoni Cytoplasmic Function of Mutant Promyelocytic Leukemia (PML) and PML-Retinoic Acid Receptor-{alpha} J. Biol. Chem., May 19, 2006; 281(20): 14465 - 14473. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020