The promyelocytic (PML) nuclear compartment and transcription control

Wild-type promyelocytic leukemia (PML) protein and an increasingly document ed number of cellular proteins are localized within discrete nuclear struct ures known as PML nuclear bodies or PODs (potential oncogenic domains). Eve n though POD function remains elusive, the integrity, topology, and molecul ar composition of these nuclear compartments have been associated with cert ain human diseases, including cancer, autoimmunity, neurodegenerative disor ders, and viral propagation. At the molecular level, PML protein has been s hown to be a coactivator of nuclear hormone receptors, whereas its oncogeni c counterpart PML-retinoic acid receptor alpha, which promotes POD disaggre gation, has been found to activate activator protein-1 transcription in a r etinoic acid-dependent manner. Recently, we demonstrated that the CREB-bind ing protein (CBP) associates with PML protein in vitro and is recruited to the PODs in vivo in a signal-dependent manner. In exploring the consequence of this association, we proposed that POD nuclear bodies are regulatory ce llular domains where proteins such as the CBP and CBP-interacting molecules may be activated or inactivated to coordinate signal-activated cellular re sponse. This paper discusses the association of PML nuclear bodies with tra nscription control and underscores the pharmacological aspects of such an o bservation. BIOCHEM PHARMACOL 60;8:1197-1201, 2000. (C) 2000 Elsevier Scien ce Inc.