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. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: J Investig Med. 2016 Jan 11;64(2):364–368. doi: 10.1097/JIM.0000000000000218

Figure 2. Components of NF-κB and HIF E3 ligases.

Figure 2

Shown on the right is the HIF complex: The HIFα subunit in its hydroxylated form is degraded by the proteasome after ubiquitination via the Cul-2-Nedd8-pVHL complex. Pharmacological inhibition of Cul-2 neddylation using MLN4924 stabilizes cellular HIFα levels, leading to increased transcription of HIF target genes. Shown on the right is NF-κB: Activating stimuli facilitate the phosphorylation of IκB, leading to the recognition of p-IκB by the Cul-1-Nedd8-βTRCP complex, culminating in its polyubiquitination and proteasomal degradation. Pharmacological inhibition of Nedd8 conjugation by MLN4924 through inhibition of the Nedd8-activating enzyme (NAE, not shown here), prevents the activation of Cul-1, preventing the liberation of NF-κB from IκB.