SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation

School of Biomedical Science, University of St. Andrews, Fife, United Kingdom.
Molecular Cell (Impact Factor: 14.02). 09/1998; 2(2):233-9.
Source: PubMed


Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation. As a result, overexpression of SUMO-1 inhibits signal-induced activation of NF-kappaB-dependent transcription. Unlike ubiquitin modification, which requires phosphorylation of S32 and S36, SUMO-1 modification of IkappaBalpha is inhibited by phosphorylation. Thus, while ubiquitination targets proteins for rapid degradation, SUMO-1 modification acts antagonistically to generate proteins resistant to degradation.

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Available from: Manuel S. Rodriguez, Aug 22, 2014
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    • "The role of SENPs encompasses removal of SUMO from target proteins, thus reversing the effects induced by SUMOylation. Although SUMOylation shares similarities with ubiquitination, it has been shown that SUMO proteins compete with ubiquitin for substrate binding; thus, SUMOylation appears to protect target proteins from proteasomal degradation [28] [29] [30]. In addition to enhancing protein stability, SUMO proteins are involved in subcellular localization and distribution of modified proteins as well as inter-and intramolecular interactions of target substrates, which affect processes essential for normal and abnormal cellular homeostasis [31] [32] [33] [34]. "
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    • "hydrocarbon receptor; APP, amyloid precursor protein; CHDs, congenital heart diseases; CSN, COP9 signalosome; GR, glucocorticoid receptor; HSFs, heat shock factors ; IPC, ischemic preconditioning; mRNP, messenger ribonucleoparticle ; NAE, NEDD8-activating enzyme; OGD, oxygen/glucose deprivation; SENPs, sentrin-specific proteases; SUMO, Small ubiquitin-related modifier types that can interplay (crosstalk) within the same or between various proteins. For example, a signal-dependent phosphorylation of protein IkB can inhibit its sumoylation and stimulate ubiquitination [1]. Various PTMs can compete for the same amino acid residue or multiple amino acid residues can be targeted by the same PTM (e.g., serine, threonine, and tyrosine residues by phosphorylation). "
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    Preview · Article · Mar 2015 · PROTEOMICS
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    • "Like other PTMs, SUMOylation is reversible and the conjugation/deconjugation mechanisms are reminiscent of the ubiquitin pathway (Muller et al., 2001). In contrast to ubiquitination though, SUMOylation does not directly target proteins for degradation but rather regulates other functions such as nuclear localization, protein–protein interactions, transcriptional activity and, interestingly, ubiquitination itself (Desterro et al., 1998; Buschmann et al., 2000). SUMOylation was first implicated in the clock following the discovery of a SUMOylation consensus motif in BMAL1 (Cardone et al., 2005). "
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