Protein B23 is a nucleolar phosphoprotein found in higher concentrations in tumor cells than in normal cells. This protein is associated with pre- ribosomal particles and is localized in the granular region of nucleoli where ribosomes are assembled. When treated with antitumor drugs (Actinomycin D., Doxorubicin, Luzopeptins, Mitomycin C or Toyocamycin), protein B23 translocates from the nucleolus to the nucleoplasm. This result indicates that these antitumor drugs affect the protein B23 binding target in the nucleolus. The proposed experiments are designed to (1) identify the binding target of protein B23 in the nucleolus which is affected by the antitumor drugs and analyze this binding site's structure (nucleotide and amino acid sequences) which will provide information for new drug development, (2) understand the function of protein B23 (its role in ribosome synthesis of tumor cells), and (3) establish a rapid and simple immunofluorescence method using the protein B23 antibody to detect drug resistant cells, to screen antitumor drugs, and monitor drug efficacy. Our long term goals are to understand the differences between the ribosome maturation processes in normal and cancer cells, to study the effects of antitumor drugs on ribosome synthesis and maturation, and to provide information for development of new inhibitors or competitors for ribosome synthesis which could be helpful in chemotherapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Experimental Therapeutics Subcommittee 2 (ET)
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Baylor College of Medicine
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Chan, P K; Chan, F Y (1999) A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin. Biochem Pharmacol 57:1265-73
Chan, P K; Chan, F Y; Morris, S W et al. (1997) Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region. Nucleic Acids Res 25:1225-32
Finch, R A; Revankar, G R; Chan, P K (1997) Structural and functional relationships of toyocamycin on NPM-translocation. Anticancer Drug Des 12:205-15
Chan, P K; Qi, Y; Amley, J et al. (1996) Quantitation of the nucleophosmin/B23-translocation using imaging analysis. Cancer Lett 100:191-7
Finch, R A; Chan, P K (1996) ATP depletion affects NPM translocation and exportation of rRNA from nuclei. Biochem Biophys Res Commun 222:553-8
Finch, R A; Chang, D C; Chan, P K (1995) GTP gamma S restores nucleophosmin (NPM) localization to nucleoli of GTP-depleted HeLa cells. Mol Cell Biochem 146:171-8
Chan, P K; Chan, F Y (1995) Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. Biochim Biophys Acta 1262:37-42
Liu, Q R; Chan, P K (1993) Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome. DNA Cell Biol 12:149-56
Finch, R A; Revankar, G R; Chan, P K (1993) Nucleolar localization of nucleophosmin/B23 requires GTP. J Biol Chem 268:5823-7
Chan, P K (1992) Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with selected cytotoxic agents (studies of B23-translocation mechanism). Exp Cell Res 203:174-81

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