The ubiquitin conjugation system regulates the canonical NF-κB activation pathway, which mediates immune responses. Linear polyubiquitin chains—in which the C terminal glycine of ubiquitin is conjugated to the α-amino group of the amino-terminal methionine of another ubiquitin—are generated by a unique ubiquitin ligase complex called linear ubiquitin chain assembly complex (LUBAC) composed of two RING domain proteins called HOIL-1 and HOIP. This is one of three complementary studies identifying a novel component of the LUBAC complex called SHARPIN, which is recruited to receptor signalling complexes (RSCs) that form after TNF and CD40L stimulation. The LUBAC complex containing SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo and is required for the activation of NF-κB signalling.
- Fumiyo Ikeda
- Yonathan Lissanu Deribe
- Ivan Dikic
