| Direct interaction of tumor suppressor CEACAM1 with beta catenin: identification of key residues in the long cytoplasmic domain. | |
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MedLine Citation:
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PMID: 18445773 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CEACAM1-4L (carcinoembryonic antigen cell adhesion molecule 1, with 4 extracellular Ig-like domains and a long, 71 amino acid cytoplasmic domain) is expressed in epithelial cells and activated T-cells, but is down-regulated in most epithelial cell cancers and T-cell leukemias. A highly conserved sequence within the cytoplasmic domain has ca 50% sequence homology with Tcf-3 and -4, transcription factors that bind beta-catenin, and to a lesser extent (32% homology), with E-cadherin that also binds beta-catenin. We show by quantitative yeast two-hybrid, BIAcore, GST-pull down, and confocal analyses that this domain directly interacts with beta-catenin, and that H-469 and K-470 are key residues that interact with the armadillo repeats of beta-catenin. Jurkat cells transfected with CEACAM1-4L have 2-fold less activity in the TOPFLASH reporter assay, and in MCF7 breast cancer cells that fail to express CEACAM1, transfection with CEACAM1 and growth in Ca2+ media causes redistribution of beta-catenin from the cytoplasm to the cell membrane, demonstrating a functional role for the long cytoplasmic domain of CEACAM1 in regulation of beta-catenin activity. |
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Authors:
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Lan Jin; Yun Li; Charng-Jui Chen; Mark A Sherman; Keith Le; John E Shively |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-04-29 |
Journal Detail:
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Title: Experimental biology and medicine (Maywood, N.J.) Volume: 233 ISSN: 1535-3702 ISO Abbreviation: Exp. Biol. Med. (Maywood) Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-24 Completed Date: 2008-07-24 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 100973463 Medline TA: Exp Biol Med (Maywood) Country: United States |
Other Details:
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Languages: eng Pagination: 849-59 Citation Subset: IM |
Affiliation:
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Division of Immunology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Rd., Duarte, CA 91010, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Antigens, CD / analysis, metabolism* Breast Neoplasms / metabolism, pathology Cell Adhesion Molecules / analysis, metabolism* Humans Jurkat Cells Leukemia, T-Cell / metabolism, pathology Models, Molecular Molecular Sequence Data Protein Binding Protein Interaction Domains and Motifs* Signal Transduction T-Lymphocytes / metabolism*, pathology Transcriptional Activation Transfection Tumor Cells, Cultured beta Catenin / analysis, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA 84202/CA/NCI NIH HHS; R01 CA084202-08/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/CD66 antigens; 0/Cell Adhesion Molecules; 0/beta Catenin |
| Comments/Corrections | |
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