Nucleic Acids Research, Vol 26, Issue 2 486-489, Copyright © 1998 by Oxford University Press
W Bruening, B Giasson, W Mushynski and HD Durham
The immediate/early promoter/enhancer of cytomegalovirus (CMV promoter) is
one of the most commonly used promoters for expression of transgenes in
eukaryotic cells. In practice, the CMV promoter is often thought of as a
constitutively active unregulated promoter. However, we have observed that
transcription from the CMV promoter can be up-regulated by a variety of
environmental stresses. Many forms of cellular stress stimulate MAP kinase
signalling pathways, resulting in activation of stress-activated protein
kinases [SAPKs, also called Jun N-terminal kinases (JNKs)] and p38 kinases.
We have found that the same conditions that lead to activation of SAPK/JNKs
and p38 kinases can also dramatically increase expression from the CMV
promoter. Inhibitors of p38 kinases abolished basal transcription from the
CMV promoter and completely blocked stress-induced up-regulation of the CMV
promoter. Overexpression of a dominant negative JNK kinase had no effect on
basal transcription, but significantly reduced up-regulation caused by
stress. These results have grave implications for use of the CMV promoter.
If the CMV promoter can be up-regulated by cellular stresses, inadvertent
activation of the stress kinase pathways may complicate, if not invalidate,
the interpretation of a wide range of experiments.
ARTICLES
Activation of stress-activated MAP protein kinases up-regulates expression of transgenes driven by the cytomegalovirus immediate/early promoter
Department of Neurotoxicology, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
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