Identifiers
NAME:RBCK1:RNF31:SHARPIN
Maps_Modules
References
PMID:24699077
LUBAC, linear ubiquitin chain assembly complex comprises????SHANK-associated RH-domain interactor (SHARPIN), heme-oxidized IRP2 ubiquitin ligase 1 homolog (HOIL1/RBCK1) and the E3 HOIL-1???interacting protein (HOIP/RNF31)
???is recruited to the TNFR1 complex via binding to the autoubiquitinated c-IAP1 and c-IAP2 proteins to mediate the assembly of linear polyubiquitin chains on NF-??B essential modifier (NEMO/IKBKG) and RIPK1
PMID:21232017, PMID:21133840, PMID:17301840
cIAP1 and cIAP2 modify RIP1, TRAF2 and
themselves with K63-linked ubiquitin chains. This creates docking sites for the LUBAC complex, an E3 ligase capable of forming linear polyubiquitin chains. The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex, which by help of its IKK2 subunit also interacts
with TRADD-bound TRAF2. In parallel, the TAK1-TAB 2 complex interacts with K63-ubiquitin modi???ed RIP1 by use of the K63-ubiquitin binding TAB 2 subunit. TAK1 become activated and then phosphorylates and activates IKK2 which in turn now phosphorylates IjBa, marking it
for K48-ubiquitination and proteasomal degradation.
PMID:24958845
NFkB activation (IkBa degradation) downstream of TNF is LUBAC-dependent.