title: Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM.
abstract: Mutations of the gene for nucleophosmin (NPM1) are the most frequent genetic aberration in patients with acute myeloid leukemia (AML). The mechanism of leukemic transformation in this leukemia subtype is not fully understood, but aberrant cytoplasmic localization of mutated NPM (NPMmut) is widely considered as an important factor for leukemia manifestation. We analyzed the subcellular localization of three types of NPM with a C-terminal mutation (A, B and E). Genes for the individual NPM forms were fused with a gene for one of fluorescent protein variants in plasmids, which were transfected into three cell lines with different endogenous NPM expression. Subcellular localization of the fluorescent protein-labeled NPM was further correlated with the relative expression of all NPM forms. We confirmed a high cytoplasmic expression of NPMmutA and NPMmutB whereas a substantial fraction of NPMmutE was found to be localized in nucleoli. Moreover, we revealed that the localization of fluorescently labeled NPM is affected by the interaction between various forms of the protein.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors.forename: Barbora
authors.identifier: http://orcid.org/0000-0002-3703-594X
authors.initials: B
authors.lastname: Brodská
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Kráčmarová
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Holoubek
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kuželová
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D011485:Protein Binding; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin