SCF-beta-TRCP ubiquitinates p-7S-p100:RELB in active NIK:p-176,S180-IKKA dimer:p-7S-p100:SCF-beta-TRCP

Stable Identifier
R-HSA-5607725
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Ubiquitination of p100 is very specific. Lysine residue K855 has been identified as the anchoring site for ubiquitin and required for signaling mediated processing of p100 to p52. In the presence of SCF-beta-TRCP E3 ligase the ubiquitin (Ub) conjugated to E2 (E2-Ub thioester) is attached to p100 at K855 (Amir et al. 2004). Several rounds of ubiquitin conjugation can produce long chains of ubiquitin moieties (polyubiquitylation), the first of which is covalently bound to p100. At this point the polyubiquitylated p100 is committed to association with, and unfolding and processing by, the 26S proteasome (Pickart & Cohen 2004).
Efficient ubiquitination of phosphorylated p100 by SCF-beta-TRCP E3 ligase also requires the presence of the components of the NEDD8 pathway: UBA3 (NEDD8-activating enzyme E1 catalytic subunit), UBC12 (NEDD8-conjugating enzyme Ubc12 (E2)), NEDD8 (Neural precursor cell expressed developmentally down-regulated protein 8). NEDD8 binds and promotes a conformational change in CUL1 that may result in efficient formation of an E2-E3 complex, thus stimulating SCF complexes activity (Kawakami et al. 2001, Morimoto et al. 2000, Read et al. 2000).
Participants
Participates
Catalyst Activity

ubiquitin-protein transferase activity of Active NIK:p-176,S180-IKKA dimer:p-7S-p100:SCF-beta-TRCP [cytosol]

Orthologous Events
Authored
Reviewed
Created
Cite Us!