title: Role of disorder in IκB-NFκB interaction.
abstract: The paradigmatic transcription factors of the NFκB family provide an increasingly complex view of the mechanism of signal-mediated transcriptional activation. Although the primary event, phosphorylation and subsequent ubiquitin-dependent degradation of IκBα, the inhibitor of the canonical NFκB (p50/p65), is reasonably well understood, the means whereby the activation is turned off by postinduction repression are less well understood. Recent work highlighted in this review suggests that the inhibitor IκBα participates in the "stripping" of NFκB from the DNA, and that this process relies heavily on the disordered and weakly ordered segments of IκBα. Kinetic and equilibrium measurements in vitro as well as genetic screens in vivo convincingly demonstrate not only that IκBα greatly increases the dissociation rate of NFκB from DNA but also that further control of the process is mediated by the extremely short half-life of free IκBα, doubtless a result of the overall weakly folded nature of the free protein. These studies illustrate the versatility of protein systems that use not only well-structured proteins and protein complexes but also the full range of available weakly structured and disordered states to maximize functional efficiency and metabolic control.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. dyson@scripps.edu
authors.forename: H Jane
authors.initials: HJ
authors.lastname: Dyson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Komives
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000737:chemistry*; D019913:Nuclear Localization Signals; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021381:Protein Transport; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000737:chemistry*
chemical_list: D020672:I-kappa B Proteins; D052002:NF-kappa B p50 Subunit; D019913:Nuclear Localization Signals; D051996:Transcription Factor RelA