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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yuasa, Yasuhito Homma, Miwako Kato Li, Dongxia Krebs, Edwin G. Homma, Yoshimi |
| Description | Author Affiliation: Homma MK ( Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. mkhomma@fmu.ac.jp); |
| Abstract | Mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis coli and also sporadic colorectal cancer development. By using antibodies raised against the N-terminal region of APC protein, we have detected the variable masses of endogenous APC proteins in individual cell lines established from human colorectal carcinomas caused by nonsense mutations of the gene. Phosphorylation of immunoprecipitates of full-length and truncated APC were observed in in vitro kinase reaction, indicating association of APC with protein kinase activity. The kinase activity complexed with APC was sensitive to heparin and used GTP as phosphoryl donor, suggesting an involvement of casein kinase 2 (CK2). Both CK2alpha- and beta-subunits were found to associate with APC in immunoprecipitates as well as in pull-down assays, with preferential interaction of APC with tetrameric CK2 holoenzyme. In synchronized cell populations, the association of APC with CK2 was cell cycle dependent, with the highest association in G(2)/M. Unexpectedly, APC immunoprecipitates containing full-length APC protein inhibited CK2 in vitro, whereas immunoprecipitates of truncated APC had little effect. This was confirmed by using recombinant APC, and the inhibitory region was localized to the C terminus of APC between residues 2086 and 2394. Overexpression of this fragment in SW480 cells suppressed cell proliferation rates as well as tumorigenesis. These results demonstrate a previously uncharacterized functional interaction between the tumor suppressor protein APC and CK2 and suggest that growth-inhibitory effects of APC may be regulated by inhibition of CK2. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 9 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenomatous Polyposis Coli Protein Metabolism Mutation Protein-Serine-Threonine Kinases Casein Kinase II Cell Division Dose-Response Relationship, Drug Glutathione Transferase Immunoblotting Models, Genetic Phosphorylation Precipitin Tests Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins Recombinant Proteins Time Factors Transfection Tumor Cells, Cultured Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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