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

PML is a protein involved in the t (15, 17) translocation of promyeloc ytic leukemia and is mainly localized ira nuclear bodies. Here we show that PML exerts a very powerful enhancing activity (up to 20-fold) on the transactivating proper ties of the progesterone receptor (PR) and has a similar effect on several other steroid hormone receptors. Ther e is probably a direct or indirect interaction between PR and PML sinc e when the latter was expressed at high concentrations it shifted PR i nto the nuclear bodies. Use of deletion mutants showed that both activ ation 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 suppressio n by the retinoic acid.