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

Stable Identifier
Reaction [omitted]
Homo sapiens
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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
8550590 Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha

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

J. Biol. Chem. 1996
14514672 Signal-induced ubiquitination of I kappaB Kinase-beta

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

J. Biol. Chem. 2003
9990853 Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP

Jiang, J, Spencer, E, 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

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

Proc Natl Acad Sci U S A 1995
Catalyst Activity

ubiquitin-protein transferase activity of SCF-beta-TRCP [cytosol]

Orthologous Events
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