Watowich S S, Morimoto R I
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Mol Cell Biol. 1988 Jan;8(1):393-405. doi: 10.1128/mcb.8.1.393-405.1988.
We have 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, we have 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.
我们分离出了一个编码葡萄糖反应蛋白GRP78的人类基因组克隆，并使用这个克隆基因探针以及一个克隆的HSP70基因，来研究这两个应激诱导基因在细胞代谢抑制剂作用下的表达情况。基于这组化学物质对GRP78和HSP70表达的影响，我们确定了三类应激基因诱导剂。第一类诱导GRP78表达，包括糖蛋白加工抑制剂。第二类导致GRP78和HSP70合成的协同激活，包括氨基酸类似物和重金属。第三类化学物质协同诱导GRP78并抑制HSP70表达；这类包括钙离子载体A23187和葡萄糖类似物2-脱氧葡萄糖。虽然GRP78或HSP70表达的诱导主要是由于转录激活，但抑制HSP70表达的化学物质是通过转录后调控起作用的。这些结果表明，GRP78和HSP70表达的调控是复杂的，可能取决于生理损伤的特异性和程度。
