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Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins.

1992; Springer Nature; Volume: 11; Issue: 2 Linguagem: Inglês

10.1002/j.1460-2075.1992.tb05095.x

1460-2075

Philippe Kastner, A. Perez, Yves Lutz, Cécile Rochette‐Egly, Marie‐Pierre Gaub, Béatrice Durand, Michel Lanotte, Roland Berger, Pierre Chambon,

Advanced biosensing and bioanalysis techniques

Research Article1 February 1992free access Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. P. Kastner P. Kastner Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author A. Perez A. Perez Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author Y. Lutz Y. Lutz Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author C. Rochette-Egly C. Rochette-Egly Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author M.P. Gaub M.P. Gaub Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author B. Durand B. Durand Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author M. Lanotte M. Lanotte Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author R. Berger R. Berger Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author P. Chambon P. Chambon Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author P. Kastner P. Kastner Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author A. Perez A. Perez Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author Y. Lutz Y. Lutz Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author C. Rochette-Egly C. Rochette-Egly Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author M.P. Gaub M.P. Gaub Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author B. Durand B. Durand Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author M. Lanotte M. Lanotte Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author R. Berger R. Berger Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author P. Chambon P. Chambon Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. Search for more papers by this author Author Information P. Kastner1, A. Perez1, Y. Lutz1, C. Rochette-Egly1, M.P. Gaub1, B. Durand1, M. Lanotte1, R. Berger1 and P. Chambon1 1Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, INSERM, Faculté de Médecine 11, Strasbourg, France. The EMBO Journal (1992)11:629-642https://doi.org/10.1002/j.1460-2075.1992.tb05095.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions. Previous ArticleNext Article Volume 11Issue 21 February 1992In this issue RelatedDetailsLoading ...