Nucleophosmin contains amyloidogenic regions that are able to form toxic aggregates under physiological conditions(119 visite) Di Natale C, Scognamiglio PL, Cascella R, Cecchi C, Russo A, Leone M, Penco A, Relini A, Federici L, Di Matteo A, Chiti F, Vitagliano L, Marasco D
The Faseb Journal (ISSN: 1530-6860, 1530-6860electronic), 2015 Sep; 29(9): 3689-3701.
Tipo di articolo: Journal Article,
Impact factor: 5.043, Impact factor a 5 anni: 5.639
*** IBB - CNR *** Department of Pharmacy, Diagnostica e Farmaceutica Molecolari-Società Cooperativa A Responsabilità Limitata, University of Naples Federico II, Via Mezzocannone, 16, Naples, 80134, Italy Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II, Naples, Italy Section of Biochemistry, Department of Biomedical Experimental and Clinical Sciences Mario Serio, University of Florence, Florence, Italy Institute of Biostructures and Bioimaging, Consiglio Nazionale Delle Ricerche, Naples, Italy Department of Physics, University of Genoa, Genoa, Italy Department of Medical, Oral, and Biotechnological Sciences, University of Chieti G. d'Annunzio, Chieti, Italy Institute of Molecular Biology and Pathology, Consiglio Nazionale Delle Ricerche, Rome, Italy Center for Advanced Biomaterials for Healthcare, Centro Interdipartimentale di Ricerca sui Biomateriali, Istituto Italiano di Tecnologia, Naples, Italy *Department of Pharmacy, Diagnostica e Farmaceutica Molecolari-Societa Cooperativa a Responsabilita Limitata, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples "Federico II," Naples, Italy; Section of Biochemistry, Department of Biomedical Experimental and Clinical Sciences "Mario Serio," University of Florence, Florence, Italy; Institute of Biostructures and Bioimaging, Consiglio Nazionale delle Ricerche, Naples, Italy; Department of Physics, University of Genoa, Genoa, Italy; Department of Medical, Oral, and Biotechnological Sciences, University of Chieti "G. d'Annunzio," Chieti, Italy; and Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Rome, Italy., *Department of Pharmacy, Diagnostica e Farmaceutica Molecolari-Societa Cooperativa a Responsabilita Limitata, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples "Federico II," Naples, Italy; Section of Biochemistry, Department of Biomedical Experimental and Clinical Sciences "Mario Serio," University of Florence, Florence, I
Nucleophosmin (NPM)-1 is a multifunctional protein involved in a variety of biologic processes and has been implicated in the pathogenesis of several human malignancies. To gain insight into the role of isolated fragments in NPM1 activities, we dissected the C-terminal domain (CTD) into its helical fragments. In this study, we observed the unexpected structural behavior of the peptide fragment corresponding to helix (H)2 (residues 264-277). This peptide has a strong tendency to form amyloidlike assemblies endowed with fibrillar morphology and beta-sheet structure, under physiologic conditions, as shown by circular dichroism, thioflavin T, and Congo red binding assays; dynamic light scattering; and atomic force microscopy. The aggregates are also toxic to neuroblastoma cells, as determined using 3-(4;5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and Ca(2+) influx assays. We also found that the extension of the H2 sequence beyond its N terminus, comprising the connecting loop with H1, delayed aggregation and its associated cytotoxicity, suggesting that contiguous regions of H2 have a protective role in preventing aggregation. Our findings and those in the literature suggest that the helical structures present in the CTD are important in preventing harmful aggregation. These findings could elucidate the pathogenesis of acute myeloid leukemia (AML) caused by NPM1 mutants. Because the CTD is not properly folded in these mutants, we hypothesize that the aggregation propensity of this NPM1 region is involved in the pathogenesis of AML. Preliminary assays on NPM1-Cter-MutA, the most frequent AML-CTD mutation, revealed its significant propensity for aggregation. Thus, the aggregation phenomena should be seriously considered in studies aimed at unveiling the molecular mechanisms of this pathology.-Di Natale, C., Scognamiglio, P. L., Cascella, R., Cecchi, C., Russo, A., Leone, M., Penco, A., Relini, A., Federici, L., Di Matteo, A., Chiti, F., Vitagliano, L., Marasco, D. Nucleophosmin contains amyloidogenic regions that are able to form toxic aggregates under physiological conditions.
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(47 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(20 visite) NEW ENGL J MED (ISSN: 0028-4793), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 DettagliEsporta in BibTeXEsporta in EndNote
119 Records (115 escludendo Abstract e Conferenze). Impact factor totale: 491.127 (479.864 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 515.273 (504.149 escludendo Abstract e Conferenze).