Complex regulation of heat shock- and glucose-responsive genes in human cells
The authors isolated a human genomic clone that encodes the glucose-responsive protein GRP78 and have used this cloned gene probe, together with a cloned HSP70 gene, to study the expression of both stress-induced genes in response to inhibitors of cellular metabolism. On the basis of the effects of this group of chemicals on GRP78 and HSP70 expression, the authors identified three classes of stress gene inducers. The first class induces GRP78 expression and includes inhibitors of glycoprotein processing. The second class results in coordinate activation of both GRP78 and HSP70 synthesis and includes amino acid analogs and heavy metals. Chemicals in the third class coordinately induce GRP78 and repress HSP70 expression; this class includes the calcium ionophore A23187 and the glucose analog 2-deoxyglucose. Whereas induction of GRP78 or HSP70 expression is primarily due to transcriptional activation, chemicals that repress HSP70 expression act through posttranscriptional regulation. These results reveal that the regulation of GRP78 and HSP70 expression is complex and may be dependent on the specificity and magnitude of physiological damage.
- Research Organization:
- Dept. of Biochemistry, Molecular Biology and Cell Biology, Northwestern Univ., Evanston, IL (US)
- OSTI ID:
- 7077607
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 8:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
CALMODULIN
GENE REGULATION
GENE REPRESSORS
DNA-CLONING
GLYCOPROTEINS
RNA PROCESSING
ACTIVATION ANALYSIS
AMINO ACIDS
ANIMAL CELLS
ENZYME INHIBITORS
GENES
GLUCOSE
HEAVY IONS
HUMAN POPULATIONS
METALS
POST-TRANSLATION MODIFICATION
STRESS ANALYSIS
THERMAL SHOCK
TRANSCRIPTION FACTORS
ALDEHYDES
CARBOHYDRATES
CARBOXYLIC ACIDS
CHARGED PARTICLES
CHEMICAL ANALYSIS
CLONING
ELEMENTS
HEXOSES
IONS
MONOSACCHARIDES
NUCLEOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
POPULATIONS
PROTEINS
SACCHARIDES
550200* - Biochemistry
400101 - Activation
Nuclear Reaction
Radiometric & Radiochemical Procedures