title: Effect of PML and PML-RAR on the transactivation properties and subcellular distribution of steroid hormone receptors.
abstract: PML (promyelocytic leukemia) is a protein involved in the t (15;17) translocation of promyelocytic leukemia and is mainly localized in nuclear bodies. Here we show that PML exerts a very powerful enhancing activity (up to 20-fold) on the transactivating properties of the progesterone receptor (PR) and has a similar effect on several other steroid hormone receptors. There is probably a direct or indirect interaction between PR and PML, because when the latter was expressed at high concentrations it shifted PR into the nuclear bodies. The use of deletion mutants showed that both activation functions (AF1 and AF2) of PR as well as the coiled coil and His-Cys-rich domains of PML were required for transcriptional enhancement. The fusion protein PML-RAR which is not localized in nuclear bodies, also enhanced the transactivating activity of PR, but this effect was totally suppressed by the administration of retinoic acid. PML, which is ubiquitously expressed, may thus be involved in the transactivation properties of steroid hormone receptors. This mechanism may also play a role in the oncogenic properties of PML-RAR and in their suppression by retinoic acid.
authors.affiliation: INSERM U-135 Hormones et Reproduction Hôpital Bicêtre.
authors.forename: A
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: J F
authors.initials: JF
authors.lastname: Savouret
authors.forename: F
authors.initials: F
authors.lastname: Quignon
authors.forename: K
authors.initials: K
authors.lastname: Delabre
authors.forename: E
authors.initials: E
authors.lastname: Milgrom
authors.forename: H
authors.initials: H
authors.lastname: De The
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011980:Receptors, Progesterone / Q000235:genetics / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human