Increased cytotoxicity of soluble Fas ligand by fusing isoleucine zipper motif
T Shiraishi, K Suzuyama, H Okamoto, T Mineta… - Biochemical and …, 2004 - Elsevier
T Shiraishi, K Suzuyama, H Okamoto, T Mineta, K Tabuchi, K Nakayama, Y Shimizu…
Biochemical and biophysical research communications, 2004•ElsevierFas (CD95) ligand (FasL) has the ability to induce apoptosis in Fas-expressing glioma cells
by binding to Fas. Several molecular species have been designed to be soluble Fas ligands
for therapeutic purposes. We successfully constructed a chimeric soluble FasL by fusing an
isoleucine zipper motif for self-oligomerization and a FLAG sequence to the extracellular
domain of the human Fas ligand (FIZ-shFasL). The cytotoxic effect of FIZ-shFasL on Jurkat
cells was equivalent to that of membrane-bound FasL and approximately 10-fold stronger …
by binding to Fas. Several molecular species have been designed to be soluble Fas ligands
for therapeutic purposes. We successfully constructed a chimeric soluble FasL by fusing an
isoleucine zipper motif for self-oligomerization and a FLAG sequence to the extracellular
domain of the human Fas ligand (FIZ-shFasL). The cytotoxic effect of FIZ-shFasL on Jurkat
cells was equivalent to that of membrane-bound FasL and approximately 10-fold stronger …
Fas (CD95) ligand (FasL) has the ability to induce apoptosis in Fas-expressing glioma cells by binding to Fas. Several molecular species have been designed to be soluble Fas ligands for therapeutic purposes. We successfully constructed a chimeric soluble FasL by fusing an isoleucine zipper motif for self-oligomerization and a FLAG sequence to the extracellular domain of the human Fas ligand (FIZ-shFasL). The cytotoxic effect of FIZ-shFasL on Jurkat cells was equivalent to that of membrane-bound FasL and approximately 10-fold stronger than that of agonistic anti-Fas antibody (CH-11). Flow cytometric analysis demonstrated that the differential Fas expression of human brain tumor cell lines partially correlated with levels of apoptosis through FIZ-shFasL. The upper limit of FIZ-shFasL for safe systemic administration to rat is estimated as below 2μg/ml in plasma concentration. FIZ-shFasL could be applicable as a therapeutic agent for cancer.
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