viral dsRNA:TRL3:TICAM1 activates RIP1

RIP1 is recruited to the activated TLR receptor by binding to TICAM1(TRIF) via its RHIM motif, followed by its polyubiquitination. Polyubiquitination is possibly mediated by TRAF6 that is also recruited to TICAM1 (Cusson-Hermance N et al. 2005). Other E3-ubiquitin ligases - cIAP1 and cIAP2 - have been reported to promote polyubiquitination of RIP proteins (Bertrand MJM et al. 2011).<p> RIP3 was shown to inhibit TRIF-induced NFkB activation in dose-dependent manner when overexpressed in HEK293T cells by competing with TRIF to bind RIP1 (Meylan E et al. 2004).

RIP1通过其RHIM结构域与TICAM1（TRIF）结合而被募集至激活的TLR受体，随后发生多泛素化。多泛素化可能由也被募集至TICAM1的TRAF6介导（Cusson-Hermance N 等人，2005年）。其他E3泛素连接酶，如cIAP1和cIAP2，亦被报道可促进RIP蛋白的多泛素化（Bertrand MJM 等人，2011年）。研究发现，在HEK293T细胞中过表达RIP3可剂量依赖性地抑制TRIF诱导的NFkB激活，其机制是通过与TRIF竞争结合RIP1（Meylan E 等人，2004年）。