The oncogenic fusion tyrosine kinase nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) induces cellular transformation in anaplastic large-cell lymphomas (ALCLs) carrying the t(2;5) chromosomal translocation. Protein-protein interactions involving NPM/ALK are important for the activation of downstream signaling pathways. This study was aimed at identifying novel NPM/ALK-binding proteins that might contribute to its oncogenic transformation. Using a proteomic approach, several RNA/DNA-binding proteins were found to coimmunoprecipitate with NPM/ALK, including the multifunctional polypyrimidine tract binding protein-associated splicing factor (PSF). The interaction between NPM/ALK and PSF was dependent on an active ALK kinase domain and PSF was found to be tyrosine-phosphorylated in NPM/ALK-expressing cell lines and in primary ALK<sup>+</sup> ALCL samples. Furthermore, PSF was shown to be a direct substrate of purified ALK kinase domain in vitro, and PSF Tyr293 was identified as the site of phosphorylation. Y293F PSF was not phosphorylated by NPM/ALK and was not delocalized in NPM/ALK<sup>+</sup>cells. The expression of ALK fusion proteins induced delocalization of PSF from the nucleus to the cytoplasm and forced overexpression of PSF-inhibited proliferation and induced apoptosis in cells expressing NPM/ALK. PSF phosphorylation also increased its binding to RNA and decreased the PSF-mediated suppression of GAGE6 expression. These results identify PSF as a novel NPM/ALK-binding protein and substrate, and suggest that PSF function may be perturbed in NPM/ALK-transformed cells. © 2007 by The American Society of Hematology.
Galietta, A., Gunby, R., Redaelli, S., Stano, P., Carniti, C., Bachi, A., et al. (2007). NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma. BLOOD, 110(7), 2600-2609.
|Citazione:||Galietta, A., Gunby, R., Redaelli, S., Stano, P., Carniti, C., Bachi, A., et al. (2007). NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma. BLOOD, 110(7), 2600-2609.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma|
|Autori:||Galietta, A; Gunby, R; Redaelli, S; Stano, P; Carniti, C; Bachi, A; Tucker, P; Tartari, CG; Huang, C; Colombo, E; Pulford, K; Puttini, M; Piazza, RG; Ruchatz, H; Villa, A; Donella-deana, A; Marin, O; Perrotti, D; Gambacorti Passerini, C|
|Data di pubblicazione:||2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1182/blood-2006-01-028647|
|Appare nelle tipologie:||01 - Articolo su rivista|