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IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival
M X Wu1, Z Ao, K V Prasad
1Division of Tumor Immunology, Dana-Farber Cancer Institute, and the Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Transcription factors of the nuclear factor-kappaB/rel (NF-kappaB) family may be important in cell survival by regulating unidentified, anti-apoptotic genes. One such gene that protects cells from apoptosis induced by Fas or tumor necrosis factor type alpha (TNF), IEX-1L, is described here. Its transcription induced by TNF was decreased in cells with defective NF-kappaB activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX-1L. In support, overexpression of antisense IEX-1L partially blocked TNF-induced expression of IEX-1L and sensitized normal cells to killing. This study demonstrates a key role of IEX-1L in cellular resistance to TNF-induced apoptosis.
Insights
Nuclear factor-kappaB (NF-kappaB) regulates anti-apoptotic genes. This study identifies IEX-1L as crucial for cell survival, protecting against tumor necrosis factor alpha (TNF)-induced apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Nuclear factor-kappaB (NF-kappaB) transcription factors are implicated in cell survival.
- The precise mechanisms by which NF-kappaB regulates anti-apoptotic genes remain incompletely understood.
- Tumor necrosis factor alpha (TNF) and Fas can induce programmed cell death (apoptosis).
Purpose of the Study:
- To identify and characterize novel NF-kappaB-regulated genes involved in anti-apoptosis.
- To elucidate the role of the IEX-1L gene in cellular resistance to TNF-induced apoptosis.
Main Methods:
- Investigated TNF-induced gene transcription in cells with varying NF-kappaB activation.
- Utilized gene transfection techniques to overexpress or inhibit IEX-1L.
- Assessed cellular sensitivity to TNF-induced apoptosis.
Main Results:
- TNF-induced transcription of IEX-1L was diminished in cells with defective NF-kappaB activation.
- Cells with impaired NF-kappaB activation showed increased sensitivity to TNF-induced apoptosis.
- Transfection with IEX-1L abolished TNF-induced apoptosis in sensitive cells.
- Antisense IEX-1L overexpression partially inhibited TNF-induced IEX-1L expression and sensitized cells to TNF.
Conclusions:
- IEX-1L is a key NF-kappaB-regulated gene that confers resistance to TNF-induced apoptosis.
- IEX-1L plays a critical role in cellular survival pathways mediated by NF-kappaB.
- This finding highlights IEX-1L as a potential therapeutic target for modulating apoptosis.