Biophysics Unit (CSIC/UPV-EHU), Department of Biochemistry and Molecular Biology, University of Basque Country (UPV-EHU), POB 644, 48080 Bilbao, Spain.
FEBS Lett. 2013 Jul 11;587(14):2254-9. doi: 10.1016/j.febslet.2013.05.055. Epub 2013 Jun 4.
Nucleophosmin (NPM) is a nucleolar protein involved in ribosome biogenesis. NPM1 gene is frequently mutated in acute myeloid leukaemia (AML), correlating with aberrant cytoplasmic localization of the protein. NPM attachment to the nucleolus in physiological conditions probably depends on binding to nucleic acids, and this recognition could be altered in AML. NPM associates to guanine-rich DNA sequences, able to fold as "G-quadruplexes". We have analyzed the interaction of pentameric, full length NPM with G-rich oligonucleotides, finding that the protein binds preferentially high-order G-quadruplexes. AML-associated mutation significantly hampers DNA binding, pointing to a possible mechanism contributing to pathological mislocalization of NPM.
核仁磷酸蛋白（Nucleophosmin，NPM）是一种参与核糖体生物发生的核仁蛋白。NPM1 基因在急性髓系白血病（acute myeloid leukemia，AML）中经常发生突变，与蛋白质异常的细胞质定位相关。在生理条件下，NPM 与核仁的结合可能依赖于与核酸的结合，而这种识别在 AML 中可能会发生改变。NPM 与富含鸟嘌呤的 DNA 序列结合，能够折叠成“G-四链体”。我们分析了五聚体全长 NPM 与富含 G 的寡核苷酸的相互作用，发现该蛋白优先结合高阶 G-四链体。与 AML 相关的突变显著阻碍了 DNA 结合，这可能是导致 NPM 病理性定位错误的一种机制。
