Regulation of differentiation by a PHD domain in the NUP98-PHF23 fusion protein.
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.
Reader
Jocelyn C
JC
Department of Pathology, University of Maryland, School of Medicine, 10 S. Pine St., MSTF-717, Baltimore, MD, USA.
Leng
Qixin
Q
Rassool
Feyruz V
FV
Ning
Yi
Y
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D041681:NIH 3T3 Cells; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000494:pharmacology; D017384:Sequence Deletion; D014178:Translocation, Genetic
D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D015514:Oncogene Proteins, Fusion; C523053:PHF23 protein, human; D011725:Pyridines; C431843:tris(2-pyridylmethyl)amine