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CNR: Alamanacco della Scienza


N. 6 - 26 mag 2010
ISSN 2037-4801

International info   a cura di Cecilia Migali


A new research on leukaemia

A study by Italian researchers of Ibpm-Cnr and Sapienza University of Rome published in Pnas was able to depict the complete folding pathway of the C-terminal domain of Nucleophosmin at quasi-atomic resolution. This study represents the first step towards the rational design of chemicals aimed at rescuing oncogenic mutations in acute myeloid leukaemia. The study of the folding properties of proteins whose stability is altered in specific pathologies is gaining momentum, with the possible goal of restoring the functional native structure by appropriate pharmacological chaperones. An essential pre-requisite for the design of such drugs is therefore the complete characterization of the folding of the mutated protein.
Nucleophosmin is a ubiquitously expressed protein and is one of the most represented nucleolar proteins. Mutation of the nucleophosmin gene is the most frequent genetic lesion in acute myeloid leukemia. Such mutations map at the C-terminal domain of the protein and all result in its denaturation. Stefano Gianni, Maurizio Brunori and colleagues developed a novel method to address the residual structure of proteins when populating partially folded conformations. This method has been applied to nucleophosmin and its folding pathway has been unveiled at nearly atomic resolution, providing a complete description of both the folding transition and denatured states. In the context of the fight against acute myeloid leukaemia, this work paves the way to future studies aimed at restoring the function of leukemic variants of nucelophosmin by stabilizing the native fold.

Cnr - Department of life sciences


Review abstract


Fonte: Stefano Gianni, Istituto di biologia e patologia molecolari, Roma, tel. 39 06/49910548, email stefano.gianni@uniroma1.it