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J Biol Chem, Vol. 274, Issue 26, 18625-18634, June 25, 1999

Multiple Promoter Elements Are Required for the Stimulatory Effect of Insulin on Human Collagenase-1 Gene Transcription
SELECTIVE EFFECTS ON ACTIVATOR PROTEIN-1 EXPRESSION MAY EXPLAIN THE QUANTITATIVE DIFFERENCE IN INSULIN AND PHORBOL ESTER ACTION

Stacey C. ChapmanDagger , Julio E. AyalaDagger , Ryan S. StreeperDagger , Ainsley A. Culbert§, Erin M. EatonDagger , Christina A. SvitekDagger , Joshua K. GoldmanDagger , Jeremy M. Tavaré§, and Richard M. O'BrienDagger

From the Dagger  Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232 and the § Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Several of the complications seen in patients with both type I and type II diabetes mellitus are associated with alterations in the expression of matrix metalloproteinases. To identify the cis-acting elements that mediate the stimulatory effect of insulin on collagenase-1 (matrix metalloproteinase-1) gene transcription a series of collagenase-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into HeLa cells. Multiple promoter elements, including an Ets and activator protein-1 (AP-1) motif, were required for the effect of insulin. The AP-1 motif appears to be a target for insulin signaling because it is sufficient to mediate an effect of insulin on the expression of a heterologous fusion gene, whereas the data suggest that the Ets motif acts to enhance the effect of insulin mediated through the AP-1 motif. Multiple promoter elements were also required for the stimulatory effect of phorbol esters on collagenase-CAT gene transcription, and the AP-1 motif was also a target for phorbol ester signaling. However, the cis-acting elements required for the effects of insulin and phorbol esters were not identical. Moreover, phorbol esters were a much more potent inducer of collagenase-CAT gene transcription than insulin, a difference that may be explained by selective effects of insulin and phorbol esters on AP-1 expression.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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