Regulation of differentiation by a PHD domain in the NUP98-PHF23 fusion protein

Abstract

Acute myeloid leukemia (AML) is frequently associated with chromosomal translocations. These translocations produce specific fusion genes that play crucial roles in leukemogenesis. We recently identified a novel NUP98-PHF23 fusion in AML. In this study, we attempt to determine the role of NUP98-PHF23 protein and its plant homeodomain (PHD) and coiled-coil domain in regulation of cellular differentiation and protein distribution. We provide evidence that NUP98-PHF23, through its PHD domain, impairs TPA-induced differentiation of K562 cells. While the fusion protein localizes to the nucleus, its deletion mutant without the PHD domain resides exclusively in the nucleolus, suggesting a potential link between chromatin-binding PHD domain and nuclear architecture.