Kataoka T, Schröter M, Hahne M, Schneider P, Irmler M, Thome M, Froelich C J, Tschopp J
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
J Immunol. 1998 Oct 15;161(8):3936-42.
FLICE-inhibitory protein, FLIP (Casper/I-FLICE/FLAME-1/CASH/CLARP/MRIT), which contains two death effector domains and an inactive caspase domain, binds to FADD and caspase-8, and thereby inhibits death receptor-mediated apoptosis. Here, we characterize the inhibitory effect of FLIP on a variety of apoptotic pathways. Human Jurkat T cells undergoing Fas ligand-mediated apoptosis in response to CD3 activation were completely resistant when transfected with FLIP. In contrast, the presence of FLIP did not affect apoptosis induced by granzyme B in combination with adenovirus or perforin. Moreover, the Fas ligand, but not the perforin/granzyme B-dependent lytic pathway of CTL, was inhibited by FLIP. Apoptosis mediated by chemotherapeutic drugs (i.e., doxorubicin, etoposide, and vincristine) and gamma irradiation was not affected by FLIP or the absence of Fas, indicating that these treatments can induce cell death in a Fas-independent and FLIP-insensitive manner.
Fas相关死亡结构域样白细胞介素-1β转化酶抑制蛋白（FLIP，又名Casper/I-FLICE/FLAME-1/CASH/CLARP/MRIT）含有两个死亡效应结构域和一个无活性的半胱天冬酶结构域，它与FADD和半胱天冬酶-8结合，从而抑制死亡受体介导的细胞凋亡。在此，我们阐述了FLIP对多种凋亡途径的抑制作用。用FLIP转染后，因CD3激活而经历Fas配体介导凋亡的人Jurkat T细胞具有完全抗性。相反，FLIP的存在并不影响颗粒酶B与腺病毒或穿孔素联合诱导的细胞凋亡。此外，FLIP抑制Fas配体，但不抑制细胞毒性T淋巴细胞的穿孔素/颗粒酶B依赖性裂解途径。化疗药物（即阿霉素、依托泊苷和长春新碱）和γ射线介导的细胞凋亡不受FLIP或Fas缺失的影响，这表明这些处理能够以Fas非依赖性和FLIP不敏感的方式诱导细胞死亡。
