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.
Aurelium Biopharma Inc. | Date: 2010-04-21
Disclosed are methods for diagnosing breast cancer in a cell sample by detecting an increase in the levels of expression of protein markers in the cell sample as compared to the levels of expression of the same protein markers in a normal, nonneoplastic breast cell sample, wherein the protein markers are selected from the group consisting of cvtokeratin 19, cathepsin D, ezrin, A-CRABPII, slc9a3r1 and HER- 2. Also disclosed is a device for the diagnosis of breast cancer in a cell sample.