受体相互作用的丝氨酸/苏氨酸 - 蛋白激酶1（RIPK1）可以是细胞死亡和存活信号复合物的一部分。无论是凋亡，坏凋亡或NFκB信号传导的ripk1是否依赖于蜂窝织背景上的自分泌/旁静脉信号，并通过RIP1本身的后期修改紧密调节。RIPK1的Pro-survival函数通过较多泛素来实现，所述多化是募集信号传导分子/络合物，例如IKK综合体和TAB2：TAK1复合物，以介导NFκB信号传导的激活（EA CK等，2006）。Cyld介导的RIPK1的脱水培养化将其取存功能切换到Caspase介导的促凋亡信号传导（Fujikura D等人2012; Moquin DM等，2013）。人和啮齿动物细胞中的Caspase-8（Casp8）有利于激酶RIPK1和RIPK3的裂解，防止ripk1 / ripk3依赖性的粪便（林Y等人。1999; Hopkins-Donaldson S等人。2000;牛顿k等人2019; Zhang X等人。2019; Lalaoui N等人.2020）。Casp8介导的人RiPK1介导的D324（小鼠D325）中的人RIPK1分离氨基末端激酶结构域通过通过羧基末端死亡结构域的二聚化来将氨基末端激酶结构域从分子的羧基 - 末端部分分离，并导致解离复杂Tradd：TRAF2：RIP1：FADD：CASP8（Lin Y等人1999; Meng H等人2018）。The lack of CASP8 proteolytic activity in the presence of viral (e.g. CrmA and vICA) or pharmacological caspase inhibitors results in necroptosis induction via RIPK1 and RIPK3 (Tewari M & Dixit VM 1995; Fliss PM & Brune W 2012; Hopkins-Donaldson S et al. 2000). Cellular FLICE-like inhibitory protein (cFLIP), which is an NF-κB target gene, form heterodimer with procaspase-8 and inhibits activation of CASP8 within the the TRADD:TRAF2:RIP1:FADD:CASP8:FLIP complex (Yu JW et al. 2009; Pop C et al. 2011). The presence of cFLIP (long form) limits CASP8 to cleave CASP3/7 but allow cleavage of RIPK1 to cause the dissociation of the TRADD:TRAF2:RIP1:FADD:CASP8, thereby inhibiting both apoptosis and necroptosis (Boatright KM et al. 2004; Yu JW et al. 2009; Pop C et al. 2011; Feoktistova M et al. 2011). Mice that lack CASP8 or knock-in mice that express catalytically inactive CASP8 (C362A) die in a RIPK3- and MLKL-dependent manner during embryogenesis (Kaiser WJ et al. 2011; Newton K et al. 2019). Studies using mice that express RIPK1(D325A), in which the CASP8 cleavage site Asp325 had been mutated, further confirmed that cleavage of RIPK1 by CASP8 is a mechanism for dismantling death-inducing complexes for limiting aberrant cell death in response to stimuli (Newton K et al. 2019; Lalaoui N et al. 2020). Disrupted cleavage of RIPK1 variants with mutations at D324 by CASP8 in humans leads to an autoinflammatory response by promoting the activation of RIPK1 (Tao P et al. 2020; Lalaoui N et al. 2020).
