Feng, Z. H., Hu, W. W., De Stanchina, E., Teresky, A. K., Jin, S. K., Lowe, S. W., Levine, A. J. (April 2007) The regulation of AMPK beta 1, TSC2, and PTEN expression by p53: Stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Research, 67 (7). pp. 3043-3053. ISSN 0008-5472
Abstract
The insulin-like growth factor 1 (IGF-1)-AKT-mTOR pathways sense the availability of nutrients and mitogens and respond by signaling for cell growth and division. The p53 pathway senses a variety of stress signals which will reduce the fidelity of cell growth and division, and responds by initiating cell cycle arrest, senescence, or apoptosis. This study explores four p53-regulated gene products, the beta 1 and beta 2 subunits of the XMPK, which are shown for the first time to be regulated by the p53 protein, TSC2, PTEN, and IGF-BP3, each of which negatively regulates the IGF-1-AKT-mTOR pathways after stress. These gene products are shown to be expressed under p53 control in a cell type and tissue-specific fashion with the TSC2 and PTEN proteins being coordinately regulated in those tissues that use insulin-dependent energy metabolism (skeletal muscle, heart, white fat, liver, and kidney). In addition, these genes are regulated by p53 in a stress signal-specific fashion. The mTOR pathway also communicates with the p53 pathway. After glucose starvation of mouse embryo fibroblasts, AMPK phosphorylates the p53 protein but does not activate any of the p53 responses. Upon glucose starvation of E1A-transformed mouse embryo fibroblasts, a p53-mediated apoptosis ensues. Thus, there is a great deal of communication between the p53 pathway and the IGF-1-AKT and mTOR pathways.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE TUMOR-SUPPRESSOR S6 KINASE IN-VIVO POSTTRANSLATIONAL MODIFICATIONS TRANSCRIPTION FACTOR AUTOPHAGY GENE DIRECT TARGET DNA-DAMAGE GROWTH |
| Subjects: | diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | CSHL Librarian |
| Date: | April 2007 |
| Date Deposited: | 09 Nov 2011 20:40 |
| Last Modified: | 23 Mar 2018 16:49 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15661 |
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