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J Biol Chem, Vol. 274, Issue 44, 31139-31144, October 29, 1999
From the The gene for the amino acid biosynthetic activity
asparagine synthetase (AS) is induced by both amino acid and glucose
deprivation of cells. The data reported here document that the human AS
gene is induced following activation of the Unfolded
Response Pathway (UPR), also known as the
Endoplasmic Reticulum Stress
Response (ERSR) in mammals. Increased AS transcription
occurs in response to glucose deprivation, tunicamycin, or
azetidine-2-carboxylate, all known to activate the UPR/ERSR pathway.
Previously identified ERSR target genes contain multiple copies of a
single highly conserved cis-element. In contrast, the human
AS gene does not contain the ERSR element, as it has been described for
other responsive genes. Instead, AS induction requires an Sp1-like
sequence, a sequence previously shown to be associated with amino acid
control of transcription, and possibly, a third region containing no
consensus sequences for known transcription factors. Oligonucleotides
covering each of these regions form DNA-protein complexes in
vitro, and for some the amount of these complexes is greater when
nuclear extracts from glucose-starved cells are tested. These results
document that a wider range of metabolic activities are activated by
the UPR/ERSR pathway than previously recognized and that genomic
elements other than those already described can serve to enhance
transcription of specific target genes.
Activation of the Unfolded Protein Response Pathway Induces Human
Asparagine Synthetase Gene Expression
,,,,
Department of Biochemistry and Molecular
Biology, and the § Department of Neuroscience, University of
Florida College of Medicine, Gainesville, Florida 32610
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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