RIP2 induces K63-linked ubiquitination of NEMO

RIP2 induces the K63-linked ubiquitination of NEMO at K285 and K399, positively modulating subsequent NF-kappaB activation (Abbot et al. 2007). TRAF6 E3 ligase is capable of performing this ubiquitination step when overexpressed in HEK239 cells, and this effect is blocked if RIP2 siRNA is co-transfected, but small interfering RNA (siRNA) experiments indicate that there are additional E3 ligases that can substitute for TRAF6 in NEMO ubiquitination. In addition to TRAF6, the K63-specific E2 ligase Ubc13 is required for NEMO ubiquitination suggesting a common mechanism for NEMO ubiquitination in NOD and TLR signaling.

RIP2通过在K285和K399位点诱导NEMO的K63连接泛素化，从而正向调节后续的NF-kappaB激活（Abbot等，2007年）。当在HEK239细胞中过表达时，TRAF6 E3连接酶能够执行这一泛素化步骤，若与RIP2 siRNA共转染，则此效应被阻断。小干扰RNA（siRNA）实验表明，存在可替代TRAF6进行NEMO泛素化的其他E3连接酶。除了TRAF6之外，K63特异性的E2连接酶Ubc13对于NEMO泛素化也是必需的，这表明NOD和TLR信号通路中NEMO泛素化存在一种共同的机制。