title: [RXR, a key member of the oncogenic complex in acute promyelocytic leukemia].
abstract: Acute promyelocytic leukaemia (APL) is induced by fusion proteins always implying the retinoic acid receptor RARa. Although PML-RARa and other fusion oncoproteins are able to bind DNA as homodimers, in vivo they are always found in association with the nuclear receptor RXRa (Retinoid X Receptor). Thus, RXRa is an essential cofactor of the fusion protein for the transformation. Actually, RXRa contributes to several aspects of in vivo -transformation: RARa fusion:RXRa hetero-oligomeric complexes bind DNA with a much greater affinity than RARa fusion homodimers. Besides, PML-RARa:RXRa recognizes an enlarged repertoire of DNA binding sites. Thus the association between fusion proteins and RXRa regulates more genes than the homodimer alone. Titration of RXRa by the fusion protein may also play a role in the transformation process, as well as post-translational modifications of RXRa in the complex. Finally, RXRa is required for rexinoid-induced APL differentiation. Thus, RXRa is a key member of the oncogenic complex.
authors: Institut universitaire d'hématologie, Inserm U944, Hôpital Saint-Louis, 75010 Paris, France. juliane.halftermeyer@gmail.com
authors: Juliane
authors: J
authors: Halftermeyer
authors: Morgane
authors: M
authors: Le Bras
authors: Hugues
authors: H
authors: De Thé
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D015514:Oncogene Proteins, Fusion; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein