2004
DOI: 10.1074/jbc.m408579200
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A Novel Ubiquitin-like Domain in IκB Kinase β Is Required for Functional Activity of the Kinase

Abstract: Activation of NF-B requires two highly related kinases named IKK␣ and IKK␤ that share identity in the nature and positioning of their structural domains. Despite their similarity, the kinases are functionally divergent, and we therefore sought to identify any structural features specific for IKK␣ or IKK␤. We performed bioinformatics analysis, and we identified a region resembling a ubiquitin-like domain (UBL) that exists only in IKK␤ and that we named the UBL-like domain (ULD). Deletion of the ULD rendered IKK… Show more

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Cited by 55 publications
(70 citation statements)
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References 55 publications
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“…S5D), the TBK1 variants all showed comparable activities in the context of both macromolecular and peptide substrates, indicating that the SDD and ULD domains do not strongly influence the catalysis or substrate specificity of purified TBK1 in vitro. Instead, these features appear to be maintained wholly within the KD of TBK1, a result that is in opposition to previous studies with IKK-family kinases (22)(23)(24)(25). For IKKα, IKKβ, and IKKε, this may simply reflect differential domain functionalities that evolved in addition to their apparent common structural roles.…”
Section: Discussioncontrasting
confidence: 55%
“…S5D), the TBK1 variants all showed comparable activities in the context of both macromolecular and peptide substrates, indicating that the SDD and ULD domains do not strongly influence the catalysis or substrate specificity of purified TBK1 in vitro. Instead, these features appear to be maintained wholly within the KD of TBK1, a result that is in opposition to previous studies with IKK-family kinases (22)(23)(24)(25). For IKKα, IKKβ, and IKKε, this may simply reflect differential domain functionalities that evolved in addition to their apparent common structural roles.…”
Section: Discussioncontrasting
confidence: 55%
“…While dimerization was necessary for inducible activation of IKKb, it was not necessary for kinase activity per se (Xu et al 2011). The ULD is necessary for kinase activity (May et al 2004) and also appears to cooperate with the SDD in binding to IkBa such that the appropriate serine residues within the destruction box are targeted for phosphorylation (Xu et al 2011). The resulting structural insights will hopefully lead to an improved understanding of substrate targeting by IKK.…”
Section: Structure and Regulation Of Ikkmentioning
confidence: 99%
“…Predicted leucine zipper and helix-loop-helix domains were not seen, and instead these regions formed an a-helical scaffold/dimerization domain (SDD). The other structural domains that were identified were the previously described ubiquitin-like domain (ULD) (May et al 2004) and the KD. The SDD, and in particular the portion previously thought to form a leucine zipper domain, mediates IKK dimerization, as had previously been predicted (Mercurio et al 1997;Woronicz et al 1997;Zandi et al 1997).…”
Section: Structure and Regulation Of Ikkmentioning
confidence: 99%
“…IKK␤ also has an additional ULD domain after the KD, which is absent in IKK␣. The novel ULD domain is required for the functional activity of IKK␤ and important for its substrate specificity (12,13).…”
mentioning
confidence: 99%