Abstract
FAS/Apo-1 (CD95) is an apoptosis-signaling cell surface receptor belonging to the TNF receptor family. Tumor cells resistant to Fas-mediated apoptosis have been described, but to date, the mechanisms responsible for this resistance are not well understood. We found that a series of apoptosis-resistant clones from human HUT78 lymphoma cells express a splicing variant coding for a truncated Fas molecule that lacks the intracellular death-signaling domain. The mutation responsible for the FasExo8Del expression was identified as a deletion-insertion in the intron 7/exon 8 region of the Fas gene. Moreover this mutation affects the phenotype in a dominant negative fashion, i.e., even in the presence of the normal receptor.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adult
-
Apoptosis / immunology*
-
Base Sequence
-
Cloning, Molecular
-
Cytoplasm / immunology*
-
Fas Ligand Protein
-
Humans
-
Lymphoma, T-Cell
-
Membrane Glycoproteins / chemistry
-
Membrane Glycoproteins / genetics*
-
Membrane Glycoproteins / physiology*
-
Molecular Sequence Data
-
Receptors, Tumor Necrosis Factor / chemistry
-
Receptors, Tumor Necrosis Factor / genetics
-
Receptors, Tumor Necrosis Factor / physiology
-
Signal Transduction / genetics
-
Signal Transduction / immunology*
-
Tumor Cells, Cultured
-
fas Receptor / physiology*
Substances
-
FASLG protein, human
-
Fas Ligand Protein
-
Membrane Glycoproteins
-
Receptors, Tumor Necrosis Factor
-
fas Receptor
Associated data
-
GENBANK/Z66556
-
GENBANK/Z66557
-
GENBANK/Z66558