The cytotoxic function of CD178 (Fas ligand (FasL)) is critical to the maintenance of peripheral tolerance and immune-mediated tissue pathology. The active site of FasL resides at the FasL extracellular region (FasLExt) and it functions through binding/cross-linking Fas receptor on target cells. In this study, we report that FasLExt-mediated cytotoxicity is regulated by the FasL cytoplasmic tail (FasLCyt). Deleting the N-terminal 2–70 aa (Δ70) or N-terminal 2–33 aa (Δ33) reduced the cytotoxic strength as much as 30- to 100-fold. By contrast, change in the cytotoxic strength was not observed with FasL deleted of the proline-rich domains (45–74 aa, ΔPRD) in the FasLCyt. Our study identifies a novel function of FasLCyt and demonstrates that FasL2–33, a sequence unique to FasL, is critically required for the optimal expression of FasLExt-mediated cytotoxicity.
CITATION STYLE
Jodo, S., Pidiyar, V. J., Xiao, S., Furusaki, A., Sharma, R., Koike, T., & Ju, S.-T. (2005). Cutting Edge: Fas Ligand (CD178) Cytoplasmic Tail Is a Positive Regulator of Fas Ligand-Mediated Cytotoxicity. The Journal of Immunology, 174(8), 4470–4474. https://doi.org/10.4049/jimmunol.174.8.4470
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