Nucleophosmin/B23 is a nucleolar phosphoprotein 20 times more abundant in tumor or proliferating cells than in normal or resting cells. Its putative function is assembly and/or transport of ribosomes. When tumor cells are treated with some anticancer drugs, the protein temporarily translocates from the nucleolus to the nucleoplasm. It is concluded these drugs affect the protein's binding site or transport and cause translocation. The proposed studies are designed to use the increased synthesis of nucleophosmin/B23 in cancer cells as a target for new anti- cancer drug development and to understand its role in tumor cell proliferation.
The specific aims are l) to determine the drug binding site in human leukemic cells 2)to inhibit the growth of human leukemic cells (K562) by antisense RNA/DNA 3)to understand the structure and function of nucleophosmin/B23 and its relationship with carcinogenesis and 4) to determine and characterize the human genomic DNA sequences of nucleophosmin/B23.
|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|
|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; 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|
|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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