Structure and regulation of the mouse GRP78 (BiP) promoter by glucose and calcium ionophore.

Dietary calorie restriction, also termed energy restriction, increases mean and maximum life span, reduces the incidence of tumors and increases the mean age of onset of diseases and tumors in every animal tested. Because life-span is genetically determined, we are studying the mechanisms by which energy restriction regulates the expression of genes. We found that energy restriction reduces hepatic glucose-regulated protein-78 (GRP78) and protein-94 mRNA levels by 2-3-fold in mice [Spindler et al., J. Nutr. 20 (1990) 1412-1417]. To investigate this down-regulation, we have cloned the mouse GRP78 promoter (pGRP78) and studied its regulation by glucose. The mouse pGRP78 and the previously cloned rat promoter mediate responsiveness to glucose deprivation, as well as to the calcium ionophore A23187. These studies are the first demonstration that cis-elements in the pGRP78 mediate responsiveness to glucose deprivation.