Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling phosphoprotein, mainly localized at nucleoli, that plays a key role in ribogenesis, centrosome duplication, and response to stress stimuli. Mutations at the C-terminal domain of NPM1 are the most frequent genetic lesion in acute myeloid leukemia and cause the aberrant and stable translocation of the protein in the cytoplasm. The NPM1 C-terminal domain was previously shown to bind nucleic acids. Here we further investigate the DNA binding properties of the NPM1 C-terminal domain both at the protein and nucleic acid levels; we investigate the domain boundaries and identify key residues for high affinity recognition. Furthermore, we demonstrate that the NPM1 C-terminal domain has a preference for G-quadruplex forming DNA regions and induces the formation of G-quadruplex structures in vitro. Finally we show that a specific sequence found at the SOD2 gene promoter, which was previously shown to be a target of NPM1 in vivo, is indeed folded as a G-quadruplex in vitro under physiological conditions. Our data extend considerably present knowledge on the DNA binding properties of NPM1 and suggest a general role in the transcription of genes characterized by the presence of G-quadruplex forming regions at their promoters

Federici, L., Arcovito, A., Scaglione, G. L., Scaloni, F., Lo Sterzo, C., Di Matteo, A., Falini, B., Giardina, B., Brunori, M., Nucleophosmin C-terminal leukemia-associated domain interacts with G-rich quadruplex forming DNA., <<THE JOURNAL OF BIOLOGICAL CHEMISTRY>>, 2010; 2010 (Novembre): 37138-37149 [http://hdl.handle.net/10807/15255]

Nucleophosmin C-terminal leukemia-associated domain interacts with G-rich quadruplex forming DNA.

Arcovito, Alessandro;Scaglione, Giovanni Luca;Giardina, Bruno;
2010

Abstract

Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling phosphoprotein, mainly localized at nucleoli, that plays a key role in ribogenesis, centrosome duplication, and response to stress stimuli. Mutations at the C-terminal domain of NPM1 are the most frequent genetic lesion in acute myeloid leukemia and cause the aberrant and stable translocation of the protein in the cytoplasm. The NPM1 C-terminal domain was previously shown to bind nucleic acids. Here we further investigate the DNA binding properties of the NPM1 C-terminal domain both at the protein and nucleic acid levels; we investigate the domain boundaries and identify key residues for high affinity recognition. Furthermore, we demonstrate that the NPM1 C-terminal domain has a preference for G-quadruplex forming DNA regions and induces the formation of G-quadruplex structures in vitro. Finally we show that a specific sequence found at the SOD2 gene promoter, which was previously shown to be a target of NPM1 in vivo, is indeed folded as a G-quadruplex in vitro under physiological conditions. Our data extend considerably present knowledge on the DNA binding properties of NPM1 and suggest a general role in the transcription of genes characterized by the presence of G-quadruplex forming regions at their promoters
Inglese
Federici, L., Arcovito, A., Scaglione, G. L., Scaloni, F., Lo Sterzo, C., Di Matteo, A., Falini, B., Giardina, B., Brunori, M., Nucleophosmin C-terminal leukemia-associated domain interacts with G-rich quadruplex forming DNA., <<THE JOURNAL OF BIOLOGICAL CHEMISTRY>>, 2010; 2010 (Novembre): 37138-37149 [http://hdl.handle.net/10807/15255]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/15255
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