PML nuclear body biogenesis and oligomerization-driven leukemogenesis

Abstract

Abstract. PML nuclear bodies (NBs), which are increasingly recognized as the central hub of many cellular signaling events, are superassembled spherical complexes with diameters of 0.1–2 μm. Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly. The productive RBCC oligomerization allows subsequent PML biogenesis steps, including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions. In promyelocytic leukemia, the oncoprotein PML/RARα (P/R) inhibits PML NBs assembly and leads to a full-fledged leukemogenesis. In this review, we review the recent progress in PML and acute promyelocytic leukemia fields, highlighting the protein oligomerization as an important direction of future targeted therapy.