Structure of SAP18: a ubiquitin fold in histone deacetylase complex assembly.
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.
McCallum
Scott A
SA
Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080-4990, USA.
Bazan
J Fernando
JF
Merchant
Mark
M
Yin
JianPing
J
Pan
Borlan
B
de Sauvage
Frederic J
FJ
Fairbrother
Wayne J
WJ
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
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