title: RXR is an essential component of the oncogenic PML/RARA complex in vivo.
abstract: Although PML-enforced RARA homodimerization allows PML/RARA to bind DNA independently of its coreceptor RXR, the latter was identified within the PML/RARA complex. We demonstrate that a PML/RARA mutant defective for RXR binding fails to trigger APL development in transgenic mice, although it still transforms primary hematopoietic progenitors ex vivo. RXR enhances PML/RARA binding to DNA and is required for rexinoid-induced APL differentiation. In RA-treated PML/RARA-transformed cells, the absence of RXR binding results in monocytic, rather than granulocytic, differentiation. PML/RARA enhances posttranslational modifications of RXRA, including its sumoylation, suggesting that PML-bound sumoylation enzymes target RXRA and possibly other PML/RARA-bound chromatin proteins, further contributing to deregulated transcription. Thus, unexpectedly, RXR contributes to several critical aspects of in vivo transformation.
authors.affiliation: CNRS/University Paris VII UMR 7151, laboratoire associé N11 de la Ligue contre le Cancer, Hôpital St. Louis, 1, avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Rihab
authors.initials: R
authors.lastname: Nasr
authors.forename: Laurent
authors.initials: L
authors.lastname: Pérès
authors.forename: Florence
authors.initials: F
authors.lastname: Riaucoux-Lormière
authors.forename: Nicole
authors.initials: N
authors.lastname: Honoré
authors.forename: Caroline
authors.initials: C
authors.lastname: Berthier
authors.forename: Dmitrii
authors.initials: D
authors.lastname: Kamashev
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Dominique
authors.initials: D
authors.lastname: Vitoux
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavau
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
mesh_terms: D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009857:Oncogenes; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins