Article

SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation

School of Biomedical Science, University of St. Andrews, Fife, United Kingdom.
Molecular Cell (Impact Factor: 14.46). 09/1998; 2(2):233-9.
Source: PubMed

ABSTRACT 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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    • "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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    Frontiers in Molecular Neuroscience 08/2014; 7:69. DOI:10.3389/fnmol.2014.00069 · 4.08 Impact Factor
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    • "Several studies have implicated sumoylation in regulation of stability of its target proteins [28], [29]. In order to test whether sumoylation may impact on Ago2 stability, we first compared the half-lives of wild-type Ago2, Ago2-K402R and Ago2-4KR by performing cycloheximide (CHX) time-course experiments upon transfection into HeLa cells. "
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    PLoS ONE 07/2014; 9(7):e102957. DOI:10.1371/journal.pone.0102957 · 3.23 Impact Factor
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    • "This could occur via three mechanisms: i) Stabilisation of BET-1 expression levels; ii) increase in BET-1’s affinity to acetylated histones; or iii) increase in BET-1’s capacity to access acetylated histones. i) As a small ubiquitine like modifier, SUMO can compete with ubiquitination and can protect against degradation [56]. ii) Addition of a SUMO peptide to a protein can cause conformational changes enhancing affinity for its target [57]. "
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