title: A splice variant of the C(2)H(2)-type zinc finger protein, ZNF268s, regulates NF-kappaB activation by TNF-alpha.
abstract: IkappaB kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-kappaB (NF-kappaB), is composed of multiple protein components, including IKK alpha/beta/gamma core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKK-interacting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/ 4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-alpha-induced NF-kappaB activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-alpha-induced NF-kappaB activation by interacting with the IKK complex.
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling Drug Discovery Research, Ewha Womans University, Seoul 127-750, Korea.
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kang
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Song
authors.forename: Hye In
authors.initials: HI
authors.lastname: Kim
authors.forename: Jawon
authors.initials: J
authors.lastname: Seo
authors.forename: Ja Won
authors.initials: JW
authors.lastname: Suh
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
authors.forename: Kong Ju
authors.initials: KJ
authors.lastname: Lee
authors.forename: Jaesang
authors.initials: J
authors.lastname: Kim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; C482295:ZNF268 protein, human; D051550:I-kappa B Kinase