title: Structure of SAP18: a ubiquitin fold in histone deacetylase complex assembly.
abstract: Signal transduction pathways are frequently found to repress transcription of target genes in the absence of stimulation and, conversely, to upregulate transcription in the presence of a signal. Transcription factors are central in this dual regulatory mechanism and widely use a generalized mechanism to repress transcription through recruitment of a Sin3-histone deacetylase (HDAC) complex to their binding sites on DNA. The protein SAP18 (Sin3-associated polypeptide of 18 kDa) has been shown to play a key role in gene-specific recruitment of the HDAC complex by a number of transcription factors including Gli, GAGA, and Bicoid. The solution structure of SAP18 reveals a ubiquitin-like fold with several large loop insertions relative to other family members. This fold supports the functional role of SAP18 as a protein-protein adapter module and provides insight for how SAP18 may bridge the Sin3-HDAC complex to transcription factors.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080-4990, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: McCallum
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Bazan
authors.forename: Mark
authors.initials: M
authors.lastname: Merchant
authors.forename: JianPing
authors.initials: J
authors.lastname: Yin
authors.forename: Borlan
authors.initials: B
authors.lastname: Pan
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D056970:Co-Repressor Proteins; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; C498650:SAP18 protein, human; D014157:Transcription Factors; D025801:Ubiquitin; D006655:Histone Deacetylases