Int J Biochem Mol Biol 2010;2(1):24-30
Original Article
Mutation of cysteine 21 inhibits nucleophosmin/B23 oligomerization and chaperone
activity
Panagiotis Prinos, Marie-Claude Lacoste, Judy Wong, Anne-Marie Bonneau, Elias Georges
Institute of Parasitology McGill University, Aurelium BioPharma Inc., Montreal, Quebec, Canada
Received September 29, 2010; accepted October 8, 2010; Epub October 12, 2010; published February 15, 2011
Abstract: 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 co-polymerize 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. (IJBMB1009004).
Keywords: Argininosuccinate synthase; arginine metabolism; nitric oxide; arginase; urea cycle, arginine recycling
Full Text PDF
Address all correspondence to:
Elias Georges,
Institute of Parasitology, McGill University.
21,111 Lakeshore Road, Ste Anne de Bellevue
Quebec, Canada, H9X 1C0
Tel: (514) 398 8137; Fax: (514) 398 7857
E-mail: elias.georges@mcgill.ca
Original Article
Mutation of cysteine 21 inhibits nucleophosmin/B23 oligomerization and chaperone
activity
Panagiotis Prinos, Marie-Claude Lacoste, Judy Wong, Anne-Marie Bonneau, Elias Georges
Institute of Parasitology McGill University, Aurelium BioPharma Inc., Montreal, Quebec, Canada
Received September 29, 2010; accepted October 8, 2010; Epub October 12, 2010; published February 15, 2011
Abstract: 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 co-polymerize 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. (IJBMB1009004).
Keywords: Argininosuccinate synthase; arginine metabolism; nitric oxide; arginase; urea cycle, arginine recycling
Full Text PDF
Address all correspondence to:
Elias Georges,
Institute of Parasitology, McGill University.
21,111 Lakeshore Road, Ste Anne de Bellevue
Quebec, Canada, H9X 1C0
Tel: (514) 398 8137; Fax: (514) 398 7857
E-mail: elias.georges@mcgill.ca
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