Related Experiment Videos
Soluble Fas/Apo-1 splicing variants and apoptosis
1Department of Immunobiology, Institute of Cell Biology, National Research Council, Rome, Italy.
Abstract:
In addition to the full length mRNA activated human peripheral blood mononuclear cells (PBMC) and T cell tumor lines express several alternatively spliced Fas variants. At least five of these code for soluble Fas (CD95) molecules. In vitro studies suggest that these soluble Fas isoforms inhibit apoptosis induced by agonistic antibodies and, more importantly, by the natural Fas ligand in Fas-bearing sensitive cells. Interestingly, this functional property can be assigned to the first 49 aminoacids of the mature protein, the only region shared by the soluble Fas molecules.
Insights
Activated human cells produce soluble Fas (CD95) variants that can inhibit programmed cell death (apoptosis). These soluble Fas isoforms block apoptosis induced by natural Fas ligand in sensitive cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Activated human peripheral blood mononuclear cells (PBMC) and T cell tumor lines express Fas.
- Several alternatively spliced Fas variants are produced, including those encoding soluble Fas (CD95) molecules.
Purpose of the Study:
- To investigate the functional properties of alternatively spliced Fas variants.
- To determine the role of soluble Fas isoforms in apoptosis regulation.
Main Methods:
- Analysis of mRNA splicing in activated human PBMC and T cell lines.
- In vitro studies to assess the effect of soluble Fas isoforms on apoptosis.
Main Results:
- At least five alternatively spliced Fas variants code for soluble Fas (CD95) molecules.
- Soluble Fas isoforms inhibit apoptosis induced by agonistic antibodies and natural Fas ligand.
- The inhibitory function of soluble Fas is localized to the first 49 amino acids of the mature protein.
Conclusions:
- Alternatively spliced Fas variants, particularly soluble Fas isoforms, play a significant role in regulating apoptosis.
- The N-terminal region of soluble Fas is crucial for its anti-apoptotic activity.