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BRE: a modulator of TNF-alpha action
1Department of Cell Biology & Anatomy, Cornell University Medical College, New York, New York 10021, USA.
Summary
The BRE gene, highly expressed in the brain, interacts with the p55 tumor necrosis factor alpha (TNF) receptor. This interaction may modulate TNF-alpha signaling pathways, impacting cellular responses.
Area of Science:
- Molecular Biology
- Cell Signaling
- Genetics
Background:
- The BRE gene is a stress-responsive gene with unknown function, highly expressed in brain and reproductive tissues.
- BRE is down-regulated by DNA damaging agents and retinoic acid, suggesting a role in cellular stress response.
- The human BRE gene encodes a 44 kDa protein, showing no homology to known genes.
Purpose of the Study:
- To identify the function of the BRE gene.
- To investigate the interaction of BRE with other proteins.
- To determine BRE's role in tumor necrosis factor alpha (TNF) signaling.
Main Methods:
- Yeast two-hybrid screening using the p55 TNF receptor juxtamembrane domain.
- In vitro biochemical assays with recombinant fusion proteins.
- Co-immunoprecipitation in transfected mammalian cells.
Main Results:
- BRE was identified as an interacting partner of the p55 TNF receptor in yeast two-hybrid screens.
- The interaction between BRE and p55 TNF receptor was confirmed by in vitro and co-immunoprecipitation assays.
- BRE specifically interacted with p55 TNF receptor, but not with other TNF family members.
- Overexpression of BRE inhibited TNF-alpha-induced NF-kappaB activation.
Conclusions:
- The BRE protein interacts with the cytoplasmic region of the p55 TNF receptor.
- This interaction suggests that BRE modulates signal transduction pathways initiated by TNF-alpha.
- BRE may play a role in regulating cellular responses to TNF-alpha, particularly NF-kappaB activation.