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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1634-1643. Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-04-081125. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-081125v1 111/3/1634    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 van Wageningen, S. Articles by Jansen, J. H. Search for Related Content PubMed PubMed Citation Articles by van Wageningen, S. Articles by Jansen, J. H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 2, 2007 Accepted November 8, 2007 Gene transactivation without direct DNA-binding defines a novel gain-of-function for PML-RAR Sake van Wageningen, Marleen C Breems-de Ridder, Jeannet Nigten, Gorica Nikoloski, Claudia A.J. Erpelinck-Verschueren, Bob Lowenberg, Theo de Witte, Daniel G. Tenen, Bert A. van der Reijden, and Joop H. Jansen* Central Hematology Laboratory and Dept. of Hematology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Institute of Hematology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands Harvard Institutes of Medicine, Harvard Medical School and Harvard Stem Cell Institute, Boston, MA, United States * Corresponding author; email: j.jansen{at}chl.umcn.nl. PML-RAR is the causative oncogene in 5-10% of the cases of acute myeloid leukemia. At physiological concentrations of retinoic acid PML-RAR silences RAR target genes, blocking differentiation of the cells. At high concentrations of ligand, it (re)activates the transcription of target genes, forcing terminal differentiation. The study of RAR target genes that mediate this differentiation has identified several genes that are important for proliferation and differentiation control in normal and malignant hematopoietic cells. In this paper we show that the PML-RAR fusion protein not only interferes with the transcription of regular RAR target genes. We show that the ID1 and ID2 promoters are activated by PML-RAR but, unexpectedly, not by wild type RAR/RXR. Our data support a model in which the PML-RAR fusion protein regulates a novel class of target genes by interaction with the Sp1 and NF-Y transcription factors, without directly binding to the DNA, defining a gain-of-function for the oncoprotein. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Nasr, V. Lallemand-Breitenbach, J. Zhu, M.-C. Guillemin, and H. de The Therapy-induced PML/RARA Proteolysis and Acute Promyelocytic Leukemia Cure Clin. Cancer Res., October 15, 2009; 15(20): 6321 - 6326. [Abstract] [Full Text] [PDF] J. B. Wu, K. Chen, X.-M. Ou, and J. C. Shih Retinoic Acid Activates Monoamine Oxidase B Promoter in Human Neuronal Cells J. Biol. Chem., June 19, 2009; 284(25): 16723 - 16735. [Abstract] [Full Text] [PDF] A. Saumet, G. Vetter, M. Bouttier, E. Portales-Casamar, W. W. Wasserman, T. Maurin, B. Mari, P. Barbry, L. Vallar, E. Friederich, et al. Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia Blood, January 8, 2009; 113(2): 412 - 421. [Abstract] [Full Text] [PDF] S. van Wageningen, G. Nikoloski, G. Vierwinden, R. Knops, B. A. van der Reijden, and J. H. Jansen The transcription factor nuclear factor Y regulates the proliferation of myeloid progenitor cells Haematologica, October 1, 2008; 93(10): 1580 - 1582. [Full Text] [PDF]

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