Journal article
Downregulation of IRS-1 protein in thapsigargin-treated human prostate epithelial cells
Experimental cell research, v 289(2), pp 352-358
2003
PMID: 14499636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Thapsigargin treatment of cultured cells leads to an increase in the intracellular calcium concentration, activation of calpain, and, in some cell types, apoptosis. Using a human prostate epithelial cell line that undergoes apoptosis in the presence of thapsigargin, we find decreased levels of IRS-1 protein levels during apoptosis. Inhibition of calpain prevents this decrease in IRS-1 protein; however, inhibitors of caspases or the proteasome are ineffective in maintaining IRS-1 levels. In terms of IGF-I-related second messenger proteins, the effect of thapsigargin is specific for IRS-1 since the protein levels of IGF-I receptor β-subunit, Akt, Erk, and Shc are not affected. In addition to preventing the reduction in IRS-1, treatment of cells with calpain inhibitor II prevents apoptosis in response to thapsigargin. Finally, IRS-1 and calpain can be identified in protein complexes isolated using IRS-1-specific antibodies, indicating that calpain can associate with either IRS-1 or one of the proteins present in protein complexes that contain IRS-1. In total, these results suggest that IRS-1 may be targeted for degradation by calpain during apoptosis.
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Details
- Title
- Downregulation of IRS-1 protein in thapsigargin-treated human prostate epithelial cells
- Creators
- Hong Zhang - Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USAHenry Hoff - Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USAChristian Sell - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA
- Publication Details
- Experimental cell research, v 289(2), pp 352-358
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000185462400016
- Scopus ID
- 2-s2.0-0141676661
- Other Identifier
- 991014878168204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Oncology