title: Regulation of mIκBNS stability through PEST-mediated degradation by proteasome.
abstract: Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be removed rapidly from cells to respond properly to the next incoming signal. A nuclear IκB protein called IκBNS is known to inhibit a subset of NF-κB target genes upon its expression by NF-κB activation. Here, we show a mechanism to control the stability of mIκBNS which might be important for cells to prepare the next round signaling. We found that mIκBNS is a short-lived protein of which the stability is controlled by proteasome, independent of ubiquitylation process. We identified that the N-terminal PEST sequence in mIκBNS was critical for the regulation of stability.
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, South Korea.
authors.forename: Koog Chan
authors.initials: KC
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, South Korea.
authors.forename: Jiyeong
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, South Korea. Electronic address: kikim@sookmyung.ac.kr.
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D019913:Nuclear Localization Signals; D046988:Proteasome Endopeptidase Complex; D011506:Proteins; D011994:Recombinant Proteins; C454819:Nfkbid protein, mouse
keywords: IκBNS; NF-κB; PEST sequence; Proteasome; Ubiquitin