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Updated: Sep 27, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
Published on: January 26, 2024
Characterization of the nutrient-sensing response unit in the human asparagine synthetase promoter
Can Zhong1, Chin Chen, Michael S Kilberg
1Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Box 100245, Gainesville 32610-0245, USA.
Abstract:
Transcription from the human asparagine synthetase (A.S.) gene is increased in response to either amino acid (amino acid response) or glucose (endoplasmic reticulum stress response) deprivation. These two independent nutrient-sensing pathways converge on the same set of genomic cis -elements, referred to as nutrient sensing-response elements (NSREs) 1 and 2, within the A.S. promoter. The present report uses single-nucleotide mutagenesis to confirm that both NSRE-1 and NSRE-2 are absolutely required for gene activation and to identify the boundaries of each binding site. The core sequence of the NSRE-1 site is contained within nucleotides -68 to -60 and the NSRE-2 core sequence is within nucleotides -48 to -43. Through insertion or deletion of 5-10 nucleotides in the intervening sequence between NSRE-1 and NSRE-2, transient transfection studies with an A.S. promoter/reporter gene construct showed that the 11 bp distance between these two elements is critical. These results document that the optimal configuration is with both binding sites on the same side of the DNA helix, only one helical turn away from each other and the data provide support for the hypothesis that a larger multi-protein complex exists between the binding proteins for NSRE-1 and NSRE-2. The data also illustrate that the combination of NSRE-1 and NSRE-2, referred to as the nutrient-sensing response unit (NSRU), has enhancer activity in that it functions in an orientation- and position-independent manner, and conveys nutrient-dependent transcriptional control to a heterologous promoter.
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