title: The FBP interacting repressor targets TFIIH to inhibit activated transcription.
abstract: FUSE-binding protein (FBP) binds the single-stranded far upstream element of active c-myc genes, possesses potent transcription activation and repression domains, and is necessary for c-myc expression. A novel 60 kDa protein, the FBP interacting repressor (FIR), blocked activator-dependent, but not basal, transcription through TFIIH. Recruited through FBP's nucleic acid-binding domain, FIR formed a ternary complex with FBP and FUSE. FIR repressed a c-myc reporter via the FUSE. The amino terminus of FIR contained an activator-selective repression domain capable of acting in cis or even in trans in vivo and in vitro. The repression domain of FIR targeted only TFIIH's p89/XPB helicase, required at several stages in transcription, but not factors required for promoter selection. Thus, FIR locks TFIIH in an activation-resistant configuration that still supports basal transcription.
authors.affiliation: Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: I
authors.initials: I
authors.lastname: Collins
authors.forename: H
authors.initials: H
authors.lastname: Ge
authors.forename: D
authors.initials: D
authors.lastname: Libutti
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J M
authors.initials: JM
authors.lastname: Egly
authors.forename: D
authors.initials: D
authors.lastname: Levens
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004265:DNA Helicases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D046911:Macromolecular Substances; D010446:Peptide Fragments; D016271:Proto-Oncogene Proteins c-myc; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C410595:poly-U binding splicing factor 60KDa; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D004265:DNA Helicases