EFFECT OF PML AND PML-RAR ON THE TRANSACTIVATION PROPERTIES AND SUBCELLULAR-DISTRIBUTION OF STEROID-HORMONE RECEPTORS

PML (promyelocytic leukemia) is a protein involved in the t (15;17) tr anslocation of promyelocytic leukemia and is mainly localized in nucle ar bodies. Here we show that PML exerts a very powerful enhancing acti vity (up to 20-fold) on the transactivating properties of the progeste rone receptor (PR) and has a similar effect on several other steroid h ormone receptors, There is probably a direct or indirect interaction b etween PR and PML, because when the latter was expressed at high conce ntrations it shifted PR into the nuclear bodies, The use of deletion m utants showed that both activation functions (AF1 and AF2) of PR as we ll as the coiled coil and His-Cys-rich domains of PML were required fo r transcriptional enhancement. The fusion protein PML-RAR which is not localized in nuclear bodies, also enhanced the transactivating activi ty of PR, but this effect was totally suppressed by the administration of retinoic acid, PML, which is ubiquitously expressed, may thus be i nvolved in the transactivation properties of steroid hormone receptors , This mechanism may also play a role in the oncogenic properties of P ML-RAR and in their suppression by retinoic acid.