AI Article Synopsis
- Interferons activate various cellular responses by interacting with a single surface receptor, and this study focuses on how they trigger apoptosis, or programmed cell death.
- Using a targeted RNA interference approach, researchers found that silencing key genes involved in interferon signaling completely blocks the cell's response to interferon, highlighting their importance.
- The cFLIP gene emerged as a critical regulator of interferon-induced apoptosis, with its silencing speeding up cell death, indicating that the balance between cFLIP and caspase-8 levels is crucial for this process.
Article Abstract
Interferons induce a pleiotropy of responses through binding the same cell surface receptor. Here we investigated the molecular mechanism driving interferon-induced apoptosis. Using a nonbiased small interfering RNA (siRNA) screen, we show that silencing genes whose products are directly engaged in the initiation of interferon signaling completely abrogate the interferon antiproliferative response. Apoptosis-related genes such as the caspase-8, cFLIP, and DR5 genes specifically interfere with interferon-induced apoptosis, which we found to be independent of the activity of death ligands. The one gene for which silencing resulted in the strongest proapoptotic effect upon interferon signaling is the cFLIP gene, where silencing shortened the time of initiation of apoptosis from days to hours and increased dramatically the population of apoptotic cells. Thus, cFLIP serves as a regulator for interferon-induced apoptosis. A shift over time in the balance between cFLIP and caspase-8 results in downstream caspase activation and apoptosis. While gamma interferon (IFN-γ) also causes caspase-8 upregulation, we suggest that it follows a different path to apoptosis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571350 | PMC |
| http://dx.doi.org/10.1128/MCB.01430-12 | DOI Listing |
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