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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Curr Opin Cell Biol. 2010 Dec;22(6):828–836. doi: 10.1016/j.ceb.2010.08.004

Figure 4. Signaling at the cytoplasmic face of the TNF receptor.

Figure 4

Illustrative representation of the complex signaling network assembled upon receptor ligation by TNF ligands. Trimerization of the TNF receptor (based on [80]) recruits TRAF2 to the cytoplasmic tail of the receptor. cIAP1 and cIAP2 are subsequently recruited through the coiled-coil domain of TRAF2, and as E3 ligases cIAP1/2 (and possibly TRAF2) facilitate ubiquitination of various substrates using their RING domains. K63-linked ubiquitin chains on RIP1K serve as a platform for recruitment of proteins containing ubiquitin-binding domains such as NEMO, TAB2 and IAP proteins themselves. Loss of this ubiquitin signal by degradation of cIAPs or other means leaves RIP1K free to activate Caspase-8, in a manner that is currently not clear at a structural level. (Based upon PDB entries: 1tnr, 1ca9, 3m0a, 3hcs, 3eb6).