Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA (Articolo in rivista)
- Type
- Articolo in rivista (Classe)
- Prodotto della ricerca (Classe)
- Label
- Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA (Articolo in rivista) (literal)
- Anno
- 2013-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1093/nar/gkt001 (literal)
- Alternative label
- Chiarella, S., De Cola, A., Scaglione, G.L., Carletti, E., Graziano, V., Barcaroli, D., Lo Sterzo, C., Di Matteo, A., Di Ilio, C., Falini, B., Arcovito, A., De Laurenzi, V., Federici, L. (2013)(literal)
Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA
in Nucleic acids research; OXFORD UNIV PRESS, OXFORD OX2 6DP, (Regno Unito)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Chiarella, S., De Cola, A., Scaglione, G.L., Carletti, E., Graziano, V., Barcaroli, D., Lo Sterzo, C., Di Matteo, A., Di Ilio, C., Falini, B., Arcovito, A., De Laurenzi, V., Federici, L. (literal)
- Pagina inizio
- 3228 (literal)
- Pagina fine
- 3239 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- 42 (literal)
- Rivista
- Nucleic acids research (Rivista)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
- 5 (literal)
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Sapienza Univ Rome, Dept Biochem Sci, I-00185 Rome, Italy Univ G dAnnunzio, CeSI Ctr Excellence Aging, I-66013 Chieti, Italy Univ G dAnnunzio, Dept Expt & Clin Sci, I-66013 Chieti, Italy Univ Cattolica Sacro Cuore, Inst Biochem & Clin Biochem, Sch Med, I-00168 Rome, Italy CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy Univ Perugia, Inst Hematol, I-06100 Perugia, Italy (literal)
- Titolo
- Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA (literal)
- Abstract
- ucleophosmin (NPM1) is an abundant nucleolar protein implicated in ribosome maturation and export, centrosome duplication and response to stress stimuli. NPM1 is the most frequently mutated gene in acute myeloid leukemia. Mutations at the C-terminal domain led to variant proteins that aberrantly and stably translocate to the cytoplasm. We have previously shown that NPM1 C-terminal domain binds with high affinity G-quadruplex DNA. Here, we investigate the structural determinants of NPM1 nucleolar localization. We show that NPM1 interacts with several G-quadruplex regions found in ribosomal DNA, both in vitro and in vivo. Furthermore, the most common leukemic NPM1 variant completely loses this activity. This is the consequence of G-quadruplex-binding domain destabilization, as mutations aimed at refolding the leukemic variant also result in rescuing the G-quadruplex-binding activity and nucleolar localization. Finally, we show that treatment of cells with a G-quadruplex selective ligand results in wild-type NPM1 dislocation from nucleoli into nucleoplasm. In conclusion, this work establishes a direct correlation between NPM1 G-quadruplex binding at rDNA and its nucleolar localization, which is impaired in the acute myeloid leukemia-associated protein variants. (literal)
- Editore
- OXFORD UNIV PRESS (Editore)
- Prodotto di
- Autore CNR
- ADELE DI MATTEO (Unità di personale interno)
- Insieme di parole chiave
Incoming links:
- Prodotto
- Autore CNR di
- ADELE DI MATTEO (Unità di personale interno)
- Editore di
- OXFORD UNIV PRESS (Editore)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
- Nucleic acids research (Rivista)
- Insieme di parole chiave di