beta-TRCP ubiquitinates IkB-alpha in p-S32,33-IkB-alpha:NF-kB complex

Stable Identifier
R-HSA-5607728
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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Two major signaling steps are required for the removal of IkappaB (IkB) alpha an inhibitor of NF-kB: activation of the IkB kinase (IKK) and degradation of the phosphorylated IkB alpha. IKK activation and IkB degradation involve different ubiquitination modes; the former is mediated by K63-ubiquitination and the later by K48-ubiquitination. Mutational analysis of IkB alpha has indicated that K21 and K22 are the primary sites for addition of multiubiquitination chains while K38 and K47 are the secondary sites. In a transesterification reaction the ubiquitin is transferred from the ubiquitin-activating enzyme (E1) to an E2 ubiquitin-conjugating enzyme, which may, in turn, transfer the ubiquitin to an E3 ubiquitin protein ligase. UBE2D2 (UBC4) or UBE2D1 (UBCH5) or CDC34 (UBC3) acts as the E2 and SCF (SKP1-CUL1-F-box)-beta-TRCP complex acts as the E3 ubiquitin ligase (Strack et al. 2000, Wu et al. 2010). beta-TRCP (beta-transducin repeats-containing protein) is the substrate recognition subunit for the SCF-beta-TRCP E3 ubiquitin ligase. beta-TRCP binds specifically to phosphorylated IkB alpha and recruits it to the SCF complex, allowing the associated E2, such as UBC4 and or UBCH5 to ubiquitinate Ikappa B alpha (Baldi et al. 1996, Rodriguez et al. 1996, Scherer et al. 1995, Alkalay et al. 1995).

Literature References
PubMed ID Title Journal Year
14514672 Signal-induced ubiquitination of I kappaB Kinase-beta

Carter, RS, Pennington, KN, Ungurait, BJ, Arrate, P, Ballard, DW

J. Biol. Chem. 2003
8550590 Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha

Baldi, L, Brown, K, Franzoso, G, Siebenlist, U

J. Biol. Chem. 1996
9990853 Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP

Spencer, E, Jiang, J, Chen, ZJ

Genes Dev 1999
7479848 Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway

Alkalay, I, Yaron, A, Hatzubai, A, Orian, A, Ciechanover, A, Ben-Neriah, Y

Proc Natl Acad Sci U S A 1995
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Catalyst Activity
Title
ubiquitin-protein transferase activity of SCF-beta-TRCP [cytosol]
Physical Entity
Activity
Orthologous Events
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