title: The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1.
abstract: The transcriptional coactivator OBF-1, which interacts with Oct-1 and Oct-2 and the octamer site DNA, has been shown to be critical for development of a normal immune response and the formation of germinal centers in secondary lymphoid organs. Here we have identified the RING finger protein Siah-1 as a protein interacting specifically with OBF-1. This interaction is mediated by the C-terminal part of Siah-1 and by residues in the N-terminus of OBF-1, partly distinct from the residues required for formation of a complex with the Oct POU domains and the DNA. Interaction between Siah-1 and OBF-1 leads to downregulation of OBF-1 protein level but not mRNA, and to a corresponding reduction in octamer site-dependent transcription activation. Inhibition of the ubiquitin-proteasome pathway in B cells leads to elevated levels of OBF-1 protein. Furthermore, in immunized mice, OBF-1 protein amounts are dramatically increased in primary activated B cells, without concomitant increase in OBF-1 mRNA. These data suggest that Siah-1 is part of a novel regulatory loop controlling the level of OBF-1 protein in B cells.
authors.affiliation: Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Tiedt
authors.forename: B A
authors.initials: BA
authors.lastname: Bartholdy
authors.forename: G
authors.initials: G
authors.lastname: Matthias
authors.forename: J W
authors.initials: JW
authors.lastname: Newell
authors.forename: P
authors.initials: P
authors.lastname: Matthias
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001665:Binding Sites; D001897:Boronic Acids / Q000494:pharmacology; D002460:Cell Line; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012323:RNA Processing, Post-Transcriptional; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D015854:Up-Regulation; D016335:Zinc Fingers; D000098563:Seven in Absentia Proteins
chemical_list: D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; C423917:MG 262; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; C091546:POU2AF1 protein, human; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex