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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Teo, Jia-ling Ma, Hong Lam, Crystal Nguyen, Cu Kahn, Michael |
| Description | Author Affiliation: Teo JL ( Institute for Chemical Genomics, 600 Broadway, Suite 580, Seattle, WA 98122, USA.); |
| Abstract | Wnt/beta-catenin signaling has been shown to promote self-renewal in a variety of tissue stem cells, including neuronal stem cells and hematopoietic stem cells. However, activation of the Wnt/beta-catenin pathway promoted and inhibition of the pathway prevented differentiation of neuronal precursor cells. A clear explanation for the differential effects of Wnt/beta-catenin activation on neuronal precursors is not available at present. Presenilin-1 (PS-1) is a polytopic protein comprised of six to eight transmembrane domains. PS-1, as part of the gamma-secretase complex, is required for the intramembrane proteolysis of both amyloid precursor protein (APP) and Notch. Additionally, through interactions with beta-catenin, PS-1 is associated with modulation of Wnt/beta-catenin signaling. A familial Alzheimer's disease-associated PS-1 mutant, PS-1(L286V), causes a dramatic increase in T cell factor (TCF)/beta-catenin transcription in PC-12 cells, which prevents normal nerve growth factor (NGF)-induced neuronal differentiation and neurite outgrowth. Selective inhibition of TCF/beta-catenin/cAMP-response element-binding protein (CREB)-binding protein (CBP)-mediated transcription, but not TCF/beta-catenin/p300, with the recently described small molecule antagonist ICG-001 corrects these defects in neuronal differentiation, highlighting the importance of Wnt/beta-catenin signaling in this process. We propose that increased TCF/beta-catenin/CBP-mediated transcription, as well as a failure to switch to TCF/beta-catenin/p300-mediated transcription, play an important role in decreasing neuronal differentiation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 34 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CREB-Binding Protein Metabolism Cell Differentiation Physiology Membrane Proteins Genetics Neurons Signal Transduction Beta Catenin Animals Bicyclo Compounds, Heterocyclic Pharmacology Antagonists & Inhibitors Drug Effects DNA Primers Fluorescent Antibody Technique Immunoblotting Luciferases Models, Biological Mutation Presenilin-1 Pyrimidinones Reverse Transcriptase Polymerase Chain Reaction TCF Transcription Factors Transfection Comparative Study Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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