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Montréal, Canada

Prinos P.,Aurelium BioPharma Inc | Lacoste M.-C.,Aurelium BioPharma Inc | Wong J.,Aurelium BioPharma Inc | Bonneau A.-M.,Aurelium BioPharma Inc | And 2 more authors.
International Journal of Biochemistry and Molecular Biology | Year: 2011

Nucleophosmin (NPM/B23) is a multifunctional nucleolar protein to which both tumor-suppressor and oncogenic functions have been attributed. NPM/B23 has a variety of binding partners including ribosomes, nucleic acids, the centrosome and tumor suppressors such as p53 and p19ARF. These disparate functions are likely due to its ability to oligomerize and display molecular chaperone activity. In this report we identify a single amino acid residue, Cys21, of nucleophosmin as important for the oligomerization and chaperone activity. Mutation of Cys21 to aromatic hydrophobic residues (e.g., Phe or Try), but not to a conserved polar residue (e.g., Ser) inhibited the pentameric oligomerization of NPM/B23. However, only Phe substitution of Cys21 drastically inhibited NPM/B23 chaperone activity. Interestingly, expression of Cys21Phe mutant in MCF7 cells demonstrated that this mutant protein does not copolymerize with endogenous wild-type NPM/B23 and acts as negative dominant by destabilizing the endogenous dimer, trimer oligomerization. Taken together, the results in this study identify Cys21 as critical residue for NPM/B23 oligomerization and chaperone functions. In addition, Cys21 mutant provide a strong link between the oligomerization and chaperone functions of NPM/B23.

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