| http://www.reactome.org/bio... | rdf:type | biopax3:Evidence | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:comment | IL1 induces the poly-ubiquitination and degradation of IRAK1. This was believed to be K48-linked polyubiquitination, targeting IRAK1 for proteolysis by the proteasome, but recently IL-1R signaling has been shown to lead to K63-linked polyubiquitination of IRAK1 (Windheim et al. 2008; Conze et al. 2008), and demonstrated to have a role in the activation of NF-kappaB. IRAK1 is ubiquitinated on K134 and K180; mutation of these sites impairs IL1R-mediated ubiquitylation of IRAK1 (Conze et al. 2008). Some authors have proposed a role for TRAF6 as the E3 ubiquitin ligase that catalyzes polyubiquitination of IRAK1 (Conze et al. 2008) but this view has been refuted (Windheim et al. 2008; Xiao et al. 2008). There is stronger agreement that Pellino proteins have a role as IRAK1 E3 ubiquitin ligases. <br>Pellino1-3 possess E3 ligase activity and are believed to directly catalyse polyubiquitylation of IRAK1 (Xiao et al. 2008; Butler et al. 2007; Ordureau et al. 2008). They are capable of catalysing the formation of K63- and K48-linked polyubiquitin chains; the type of linkage is controlled by the collaborating E2 enzyme. All the Pellino proteins can combine with the E2 heterodimer UbcH13â??Uev1a to catalyze K63-linked ubiquitylation (Ordureau et al. 2008). | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:evidenceCode | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:evidence | http://www.reactome.org/bio... | lld:biopax3 |
