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

Alessandro Arcovito, Giovanni Luca Scaglione, Bruno Giardina, Luca Federici, Flavio Scaloni, Carlo Lo Sterzo, Adele Di Matteo, Brunangelo Falini, Maurizio Brunori

Risultato della ricerca: Contributo in rivistaArticolo in rivista

46 Citazioni (Scopus)

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
Lingua originaleEnglish
pagine (da-a)37138-37149
Numero di pagine12
RivistaTHE JOURNAL OF BIOLOGICAL CHEMISTRY
Volume2010
Stato di pubblicazionePubblicato - 2010

Keywords

  • Nucleophosmin
  • leukemia

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