Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DBP, HLF and TEF comprise a distinct subfamily of mammalian bZIP proteins that plays an important role in regulation of tissue-specific gene expression, particularly in the liver. In this report we demonstrate that DBP contains a 38 amino acid TAD which is highly homologous to the HLF and TEF TADs that we have delineated previously. Deletion of this domain completely abrogates transcriptional activity of native DBP and GAL4-DBP fusion proteins. This domain functions as a modular TAD that is a potent transcriptional activator when fused to the GAL4 DBD. While DBP itself is a liver-specific transactivator, the DBP TAD is active in a variety of cell types, indicating that liver-specific activity is not an intrinsic property of the TAD and must be conferred by other regions of the protein. Using GAL4-HLF fusion proteins, we further refine the core TAD of PAR proteins to a region of 13 amino acids. Recently described PAR-bZIP proteins from Drosophila and zebrafish also contain domains that share strong homology with the TAD of mammalian PAR proteins, making this one of the most highly evolutionarily conserved TADs identified to date.
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PMID:The DBP transcriptional activation domain is highly homologous to that of HLF and TEF and is not responsible for the tissue type-specific transcriptional activity of DBP. 1122 63

Insulin signaling in the liver blunts glucose production and stimulates triglyceride biosynthesis. FoxO1 is required for cAMP induction of hepatic glucose production and is permissive for the effect of insulin to suppress this process. Moreover, FoxO1 ablation increases lipogenesis. In this study, we investigated the pleiotropic actions of FoxO1 on glucose and lipid metabolism. To this end, we reconstituted FoxO1 function in mice with a liver-specific deletion of Foxo1 using targeted knock-in of an allele encoding a DNA binding-deficient FoxO1 mutant (L-DBD). Chow-reared L-DBD mice showed defects in hepatic glucose production but normal liver triglyceride content despite increased rates of de novo lipogenesis and impaired fatty acid oxidation in isolated hepatocytes. Gene expression studies indicated that FoxO1 regulates the expression of glucokinase via a cell-nonautonomous coregulatory mechanism, while its regulation of glucose-6-phosphatase proceeds via a cell-autonomous action as a direct transcriptional activator. These conclusions support a differential regulation of hepatic glucose and lipid metabolism by FoxO1 based on the mechanism by which it alters the expression of key target genes involved in each process.
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PMID:A mutant allele encoding DNA binding-deficient FoxO1 differentially regulates hepatic glucose and lipid metabolism. 2557 59