ACTIVATION OF STRESS-ACTIVATED MAP PROTEIN-KINASES UP-REGULATES EXPRESSION OF TRANSGENES DRIVEN BY THE CYTOMEGALOVIRUS IMMEDIATE EARLY PROMOTER/

The immediate/early promoter/enhancer of cytomegalovirus (CMV promoter ) is one of the most commonly used promoters for expression of transge nes in eukaryotic cells, In practice, the CMV promoter is often though t of as a constitutively active unregulated promoter. However, we have observed that transcription from the CMV promoter ca? be up-regulated by a variety of environmental stresses, Many forms of cellular stress stimulate MAP kinase signalling pathways, resulting inactivation of s tress-activated protein kinases [SAPKs, also called Jun N-terminal kin ases (JNKs)] and p38 kinases, We have found that the Same conditions t hat lead to activation of SAPK/JNKs and p38 kinases can also dramatica lly increase expression from the CMV promoter, inhibitors of p38 kinas es abolished basal transcription from the CMV promoter and completely blocked stress-induced up-regulation of the CMV promoter, Overexpressi on of a dominant negative JNK kinase had no effect on basal transcript ion, but significantly reduced up-regulation caused by stress, These r esults have grave implications for use of the CMV promoter. If the CMV promoter can be up-regulated by cellular stresses, inadvertent activa tion of the stress kinase pathways may complicate, if not invalidate,t he interpretation of a wide range of experiments.