caspase依赖的凋亡和ripk依赖的坏死之间的平衡被发现依赖于fadd样白细胞介素-1转化酶(FLICE)-抑制蛋白亚型(cFLIP,由CFLAR基因编码)的水平(在Tummers B和Green DR 2017中综述)。cFLIP有两种主要的亚型:长FLIP(L)和短FLIP(S)。FLIP(L)和FLIP(S)都在死亡诱导信号复合物(DISC)时与前蛋白酶-8二聚,如TRADD:TRAF2:RIPK1: FADD:CASP8:FLIP(L),然而它们差异地调节CASP8的激活(Pop C et al. 2011;Oberst A et al. 2011;Hughes MA et al. 2009, 2016)。FLIP(L):CASP8的异质二聚体抑制CASP8活性,限制CASP3/7的切割,但允许RIPK1的切割,导致TRADD:TRAF2:RIPK1:FADD:CASP8复合物的解离,从而抑制细胞凋亡和坏死(Pop C et al. 2011;Oberst A et al. 2011;Hughes MA et al. 2009;Lalaoui N et al 2020)。FLIP(L)的加工也发生在DISC,并依赖于CASP8活性(酶原和成熟形式)。 Upon activation FLIP(L) is cleaved to generate N‑terminal FLIP(p43) and C‑terminal FLIP(p12) (Irmler M et al. 1997; Chang DW et al. 2002; Yu JW et al. 2009; Pop C et al. 2011). FLIP(S) is a truncated version of procaspase‑8 containing tandem DEDs only. FLIP(S) acts purely as an antagonist of CASP8 activity inhibiting apoptosis. FLIP(S) has also been proposed to induce necroptosis in conditions when RIPK1 is deubiquitylated and when FLIP(L) is absent (Feoktistova M et al. 2011). Important to note that the latest statement has been shown in the context of the TLR3 signalling pathway.
Yu JW,杰弗里,PD.,施,Y
凯勒,N,母马,J,啊,他,格拉特案的裁决,毫克
流行,C,Oberst,,阻力,米,Van Raam BJ,Riedl, SJ,绿色,博士,Salvesen公司GS
Kataoka T,巴德,钢筋混凝土,叫喊,N,Thome, M,Martinon F,,M·埃姆勒,,伯恩斯,K,Hahne, M,肯尼迪,N,Kovacsovics, M,Tschopp J
Kataoka T,Tschopp J
©2021Reactome