[Effect of PML and PML-RAR on the transactivation properties and subcellular localization of steroid hormone receptors].
PML 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 since when the latter was expressed at high concentrations it shifted PR into the nuclear bodies. 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 the retinoic acid.
Guiochon-Mantel
A
A
INSERM U, 135, Hormones et Reproduction, Hôpital de Bicêtre, Le Kremlin Bicêtre.
Savouret
J F
JF
Quignon
F
F
Delabre
K
K
Milgrom
E
E
De The
H
H
D066298:In Vitro Techniques; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein