Skip to main content
. 2017 Apr 26;7(4):170026. doi: 10.1098/rsob.170026

Figure 4.

Figure 4.

TNF-induced canonical NF-κB and apoptosis pathways. Different linkage types of ubiquitin chains, Met 1-, Lys 11-, Lys 48- and Lys 63-linked ubiquitin chains, are involved in the TNF-induced canonical NF-κB signalling pathway and the TNFR complex II-dependent apoptosis pathway. Ubiquitin chains of different linkage types are generated by E3 ligases (shown in brown), such as cIAP, HOIP-containing LUBAC complex and SCF-βTrCP. These ubiquitin chains are hydrolysed by DUBs (in yellow) such as OTULIN and CYLD. A20 has a dual role as an E3 ligase and a DUB. Ubiquitination of the substrates including cIAPs, RIPK1, NEMO and IκB-α are critical for the signalling pathway. The TNFR complex II-mediated apoptosis pathway includes RIPK1, TRADD, FADD and Caspase 8. Activation of Caspase 8 leads to the Caspase 3-dependent cleavage of PARP and apoptosis. The LUBAC complex (HOIP, SHARPIN and HOIL-1L) and the CYLD-SPATA2 complex regulates the TNFR complex II-induced apoptosis pathway. Involvement of OTULIN in this apoptosis signalling pathway is not yet determined.