Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation<br>

Stable Identifier
R-HSA-975122
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endosome membrane, cytosol
ReviewStatus
5/5
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Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation<br>
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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.
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 UBE2N:UBE2V1 (Ubc13:Uev1a) to catalyze K63-linked ubiquitylation (Ordureau et al. 2008).
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Output
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as an event of
Catalyst Activity

ubiquitin-ubiquitin ligase activity of p-Pellino:hp-IRAK1:TRAF6 [endosome membrane]

Physical Entity
p-Pellino:hp-IRAK1:TRAF6 [endosome membrane] (Homo sapiens)
Activity
ubiquitin-ubiquitin ligase activity (GO:0034450)
Orthologous Events
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Bos taurus)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Canis familiaris)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Danio rerio)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Drosophila melanogaster)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Mus musculus)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Rattus norvegicus)
Pellino ubiquitinates hp-IRAK1 upon TLR7/8 or 9 activation
(Sus scrofa)
Authored
Shamovsky, V  (2010-06-01)
Reviewed
Gillespie, ME  (2010-10-29)
Created
Shamovsky, V  (2010-09-22)
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