title: A Regulated, Ubiquitin-Independent Degron in IκBα.
abstract: Whereas ubiquitin-dependent degrons have been characterized in some detail, how proteins may be targeted to ubiquitin-independent proteasomal degradation remains unclear. Here we show that IκBα contains an ubiquitin-independent degron whose activity is portable to heterologous proteins such as the globular protein GFP (green fluorescent protein) via a proteasome-dependent, ubiquitin-independent, non-lysosomal pathway. The ubiquitin-independent degradation signal resides in an 11-amino-acid sequence, which is not only sufficient but also required for IκBα's short half-life. Finally, we show that this degron's activity is regulated by the interaction with NFκB, which controls its solvent exposure, and we demonstrate that this regulation of the degron's activity is critical for IκBα's signaling functions.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Fortmann
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Lewis
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Ngo
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Riku
authors.initials: R
authors.lastname: Fagerlund
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat / Q000235:genetics*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D049452:Green Fluorescent Proteins; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D059748:Proteolysis; D015398:Signal Transduction / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D018942:Macrolides; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D025801:Ubiquitin; C057620:bafilomycin A; D000072000:NF-KappaB Inhibitor alpha; D049452:Green Fluorescent Proteins; D002738:Chloroquine; D003513:Cycloheximide
keywords: IκBα; NFκB; degron; protein half-life control; ubiquitin-independent degradation