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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, Margaret S. D'amour, Karen A. Papkoff, Jackie |
| Description | Author Affiliation: Lee MS ( Aventis Pharmaceuticals, Cambridge Genomics Center, Cambridge, MA 02139, USA.) |
| Abstract | We have developed a novel Saccharomyces cerevisiae model system to dissect the molecular events of β-catenin (β-cat) signaling. Coexpression of mammalian β-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins and a functional complex that activates reporter gene transcription from constructs containing leukocyte enhancer factor (LEF)/T cell factor (TCF) response elements. Reporter transcription is constitutive, requires expression of both β-cat and TCF4 or LEF1, and is not supported by mutated LEF/TCF binding elements or by TCF4 or LEF1 mutants. A cytoplasmic domain of E-cadherin or a functional fragment of adenomatous polyposis coli (APC) protein (APC-25) complexes with β-cat, reduces β-cat binding to TCF4, and leads to increased cytoplasmic localization of β-cat and a reduction in reporter activation. Systematic mutation of putative nuclear export signal sequences in APC-25 decreases APC-25 binding to β-cat and restores reporter gene transcription. Additional β-cat signaling components, Axin and glycogen synthase kinase 3β, form a multisubunit complex similar to that found in mammalian cells. Coexpression of the F-box protein β-transducin repeat-containing protein reduces the stability of β-cat and decreases reporter activation. Thus, we have reconstituted a functional β-cat signal transduction pathway in yeast and show that β-cat signaling can be regulated at multiple levels, including protein subcellular localization, protein complex formation, and protein stability. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 158 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2002-09-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cytoskeletal Proteins Physiology Repressor Proteins Saccharomyces Cerevisiae Metabolism Signal Transduction Trans-Activators Active Transport, Cell Nucleus Adenomatous Polyposis Coli Protein Alanine Amino Acid Substitution Axin Protein Biological Transport, Active Cadherins Calcium-Calmodulin-Dependent Protein Kinases Chemistry Cytoplasm DNA-Binding Proteins Genetics Gene Deletion Gene Expression Regulation Genes, Reporter Glycogen Synthase Kinases Lymphoid Enhancer-Binding Factor 1 Models, Biological Oligopeptides Peptides Proteins TCF Transcription Factors Transcription Factor 7-Like 2 Protein Transcription Factors Transducin Beta Catenin Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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