HMG box-containing protein 1 (HBP1) is a high mobility group (HMG) box transcription factor that negatively regulates the Wnt-beta-catenin pathway []and is involved in histone H1(0) gene expression []. It binds the transcription factor TCF4 and prevents it from binding to its target genes, including c-MYC and CYCLIN D []. It acts as a tumour suppressor and an important effector in oncogene-induced premature senescence [].
Spinocerebellar ataxia type 1 is late-onset neurodegenerative diseases caused by the expansion of a CAG triplet repeat in the SCA1 gene. This results in the lengthening of a polyglutamine tract in the gene product ataxin-1 producing a toxic gain of function that results in neuronal death. The crystal structure of the AXH domain of ataxin-1 has been determined as it exhibits significant sequence similarity to the transcription factor HBP1 []and has been implicated in RNA binding and self-association. The AXH domain is dimeric and contains an OB-fold, a structural motif found in many oligonucleotide-binding proteins. By comparison to other proteins that contain an OB-fold, the putative RNA-binding region has been identified. In addition, there are a number of well-conserved residues that form a second ligand-binding surface, suggesting that AXH domains interact with a common yet unidentified partner [].
Spinocerebellar ataxia type 1 is late-onset neurodegenerative diseases caused by the expansion of a CAG triplet repeat in the SCA1 gene. This results in the lengthening of a polyglutamine tract in the gene product ataxin-1 producing a toxic gain of function that results in neuronal death. The crystal structure of the AXH domain of ataxin-1 has been determined as it exhibits significant sequence similarity to the transcription factor HBP1 []and has been implicated in RNA binding and self-association. The AXH domain is dimeric and contains an OB-fold, a structural motif found in many oligonucleotide-binding proteins. By comparison to other proteins that contain an OB-fold, the putative RNA-binding region has been identified. In addition, there are a number of well-conserved residues that form a second ligand-binding surface, suggesting that AXH domains interact with a common yet unidentified partner [].
This domain can be found in plant bZIP transcription factors, including Arabidopsis thaliana G-box binding factor 1 (GBF1) [], Zea mays Opaque-2 []and Ocs element-binding factor 1 (OCSBF-1) [], Triticum aestivum Histone-specific transcription factor HBP1 (or HBP-1a) [], Petroselinum crispum Light-inducible protein CPRF3 and CPRF6, and Nicotiana tabacum BZI-3 [], among many others []. Opaque-2 plays a role in affecting lysine content and carbohydrate metabolism, acting indirectly on starch/amino acid ratio []. bZIP G-box binding factors (GBFs) contain an N-terminal proline-rich domain in addition to the bZIP domain. GBFs are involved in developmental and physiological processes in response to stimuli such as light or hormones [, ]. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription [].
This entry represents the paired amphipathic helix (PAH) repeat. Sin3 proteins have at least three PAH domains (PAH1, PAH2, and PAH3) [, ]. They are components of a co-repressor complex that silences transcription, playing important roles in the transition between proliferation and differentiation. Sin3 proteins are recruited to the DNA by various DNA-binding transcription factors such as the Mad family of repressors, Mnt/Rox, PLZF, MeCP2, p53, REST/NRSF, MNFbeta, Sp1, TGIF and Ume6 []. Sin3 acts as a scaffold protein that in turn recruits histone-binding proteins RbAp46/RbAp48 and histone deacetylases HDAC1/HDAC2, which deacetylate the core histones resulting in a repressed state of the chromatin []. The PAH domains are protein-protein interaction domains through which Sin3 fulfils its role as a scaffold. The PAH2 domain of Sin3 can interact with a wide range of unrelated and structurally diverse transcription factors that bind using different interaction motifs. For example, the Sin3 PAH2 domain can interact with the unrelated Mad and HBP1 factors using alternative interaction motifs that involve binding in opposite helical orientations [].Structurally, PAH2 is composed of four helices arranged in an open up-and-down bundle fold which binds α-helical peptides.
This entry represents the paired amphipathic helix (PAH) repeat. Sin3 proteins have at least three PAH domains (PAH1, PAH2, and PAH3) [, ]. They are components of a co-repressor complex that silences transcription, playing important roles in the transition between proliferation and differentiation. Sin3 proteins are recruited to the DNA by various DNA-binding transcription factors such as the Mad family of repressors, Mnt/Rox, PLZF, MeCP2, p53, REST/NRSF, MNFbeta, Sp1, TGIF and Ume6 []. Sin3 acts as a scaffold protein that in turn recruits histone-binding proteins RbAp46/RbAp48 and histone deacetylases HDAC1/HDAC2, which deacetylate the core histones resulting in a repressed state of the chromatin []. The PAH domains are protein-protein interaction domains through which Sin3 fulfils its role as a scaffold. The PAH2 domain of Sin3 can interact with a wide range of unrelated and structurally diverse transcription factors that bind using different interaction motifs. For example, the Sin3 PAH2 domain can interact with the unrelated Mad and HBP1 factors using alternative interaction motifs that involve binding in opposite helical orientations [].
Proteins in this entry contain N-terminal PAH (paired amphipathic helix) repeats, a histone deacetylase interacting domain, and a Sin3, C-terminal domain. Sin3 proteins have at least three PAH domains (PAH1, PAH2, and PAH3). They are components of a co-repressor complex that silences transcription, playing important roles in the transition between proliferation and differentiation. Sin3 proteins are recruited to the DNA by various DNA-binding transcription factors such as the Mad family of repressors, Mnt/Rox, PLZF, MeCP2, p53, REST/NRSF, MNFbeta, Sp1, TGIF and Ume6 []. Sin3 acts as a scaffold protein that in turn recruits histone-binding proteins RbAp46/RbAp48 and histone deacetylases HDAC1/HDAC2, which deacetylate the core histones resulting in a repressed state of the chromatin []. The PAH domains are protein-protein interaction domains through which Sin3 fulfils its role as a scaffold. The PAH2 domain of Sin3 can interact with a wide range of unrelated and structurally diverse transcription factors that bind using different interaction motifs. For example, the Sin3 PAH2 domain can interact with the unrelated Mad and HBP1 factors using alternative interaction motifs that involve binding in opposite helical orientations []. The Sin3, C-terminal domain forms interactions with histone deacetylases [].
