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Activation of the Human Asparagine Synthetase Gene by the Amino Acid Response and the Endoplasmic Reticulum Stress Response Pathways Occurs by Common Genomic Elements
The human asparagine synthetase ( AS ) gene is transcriptionally regulated by amino acid deprivation (amino acid response, AAR) and the endoplasmic reticulum stress response (ERSR), also known as the unfolded protein response pathway. The results reported here document the novel observation that ind...
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Published in: | The Journal of biological chemistry 2000-09, Vol.275 (35), p.26976 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | The human asparagine synthetase ( AS ) gene is transcriptionally regulated by amino acid deprivation (amino acid response, AAR) and the endoplasmic reticulum stress
response (ERSR), also known as the unfolded protein response pathway. The results reported here document the novel observation
that induction of the AS gene by the AAR and ERSR pathways occurs via the same set of genomic elements. Data supporting this conclusion include transient
transfection of AS promoter/reporter gene constructs that illustrate that the transcriptional control elements used by both
pathways are contained with nucleotides â111 to â34 of the AS promoter. In vivo footprinting analysis of this region identified six specific protein-binding sites. Within two of these sites, altered footprinting
was observed following amino acid or glucose deprivation, but the patterns were identical for both the AAR and the ERSR pathway.
Site-directed mutation of individual nucleotides within these two binding sites confirmed their importance for regulated transcription,
and none of the mutations resulted in loss of response of only one pathway. Neither of these two sites corresponds to a recently
identified ERSR cis -element, nor do they contain consensus sequences for known transcription factors. Collectively, the data document that there
are at least two independent transcriptional mechanisms for gene activation by the ERSR pathway, one of which terminates at
the same genomic elements used by the AAR pathway. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M000004200 |