Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human protein C is a liver-produced plasma anticoagulant. Four heterozygous point mutations located in the promoter region have been identified in families with type I protein C deficiency and recurrent venous thrombosis. However, detailed analysis of regulatory elements and their interacting factors remains to be undertaken. This report presents results of biochemical and functional characterizations of several cis-elements located in the 5'-upstream regulatory region and the trans-acting factors that interact with them. A cloned DNA fragment from nucleotides (nt) -418 to +45 could confer tissue specificity, whereas nt -88 to +45 was sufficient for basal promoter activity of protein C gene. Five cis-elements corresponding to HNF-1, HNF-3, and NF-I/CTF binding sites have been identified. Four heterozygous mutations have been shown to disrupt HNF-3 [mutants of A(-32)G and T(-27)A] and HNF-1 [T(-14)C and C(-10)T] binding. Mutation in the NF-I-binding site also significantly impairs the promoter activity. Viewed as a whole, these results indicate that HNF-1, HNF-3, and NF-I/CTF play critical roles in transcriptional regulation of the protein C gene.
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PMID:Characterization of human protein C gene promoter: insights from natural human mutants. 894 31

We have previously characterized the functional cis elements of the protein C promoter. One hepatocyte nuclear factor-1 (HNF-1) site, three HNF-3 sites, and at least two NF-I sites have been identified within the 140-bp basal transcriptional unit of this promoter. Here we present evidence that either HNF-1alpha or HNF-3 can cooperate with each other in binding to their cis elements. The results from the co-transfection assays in HeLa cells showed a novel synergistic transactivation between HNF-1alpha and HNF-3. Our data further indicate that the unique overlapping of the HNF-3 sites, the specific spatial relationship of the sites, and the co-activator C/EBP all contributed to the synergistic interaction. Although NF-I itself has a weak transactivating effect, it apparently coordinates the transactivation complex formation. NF-I can synergistically enhance the transactivation of HNF-1alpha or HNF-3. Taken together, the combinatorial interplay of HNF-1alpha, HNF-3, and NF-I make a significant contribution to the activation of the liver-specific protein C gene.
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PMID:Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the activation of the liver-specific protein C gene. 917 62