GAGE, an Antiapoptotic Protein Binds and Modulates the Expression of Nucleophosmin/B23 and Interferon Regulatory Factor 1
| Autor: | Louis Deiss, Fruma Yehiely, Richa Bedi, Rupinder K. Kular, Zoran M. Cilensek, Kumar Kotlo |
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| Rok vydání: | 2009 |
| Předmět: |
endocrine system
Programmed cell death Time Factors Cell Survival Blotting Western Immunology Gene Expression Apoptosis Endogeny Biology Transfection Cell Line HeLa Interferon-gamma Antigens Neoplasm Virology Humans Gene Caspase 7 Nucleophosmin Caspase 1 HEK 293 cells Nuclear Proteins Cell Biology Blotting Northern biology.organism_classification Molecular biology Neoplasm Proteins Cell biology IRF1 Hygromycin B Protein Processing Post-Translational HeLa Cells Interferon Regulatory Factor-1 Protein Binding |
| Zdroj: | Journal of Interferon & Cytokine Research. 29:645-656 |
| ISSN: | 1557-7465 1079-9907 |
| DOI: | 10.1089/jir.2008.0099 |
| Popis: | The GAGE family of highly related tumor antigens is expressed in a variety of tumors. This albeit silent gene expression resulted in resistance of cells to various apoptotic agents such as Fas, interferon-gamma, Taxol, or gamma-radiation. We now report that GAGE overexpression in either HeLa (expressing endogenous GAGE) or HEK293 (devoid of GAGE expression) rendered those cells unsusceptible to cell death induced by IFN-gamma. We investigated the underlying mechanism of GAGE-induced cell survival upon treatment with IFN-gamma in this report. We showed that GAGE overexpression resulted in down-regulation of a key player of IFN-gamma-signaling pathway, interferon regulatory factor 1 (IRF1), and its target genes caspase-1 and caspase-7. An interaction between GAGE and IRF1 is detected in cells. Furthermore, GAGE interacted with a multifunctional protein nucleophosmin (NPM)/B23 and increased its abundance by stabilizing the protein. Increased level of NPM/B23 in conjunction with decreased level of IRF1 could aid GAGE-induced resistance to IFN-gamma. Our results suggest that GAGE could rescue cell death induced by IFN-gamma by altering the level of key players in cell death pathways. As GAGE is silent in most healthy tissues, targeting GAGE could result in therapeutic interventions in cancer therapy. |
| Databáze: | OpenAIRE |
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