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Nucleic Acids Research, 1994, Vol. 22, No. 24 5184-5189
© 1994


Articles

Two separate sites contribute to AP-1 activation of the promoter for 3-hydroxy-3-methylglutaryl coenzyme A synthase

Shawn M. Vallett and Timothy F. Osborne*

Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine CA 92717-3900, USA

*To whom correspondence should be addressed

Received October 12, 1994. Accepted October 24, 1994.

Metabolic flux into the mevalonate pathway is regulated by end product repression and cell growth. In the experiments reported here the transcrlptlonal promoter for an early enzyme of the pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase, Is shown to be activated by the growth stimulatory agent tetraphorbol acetate (TPA). We show that TPA has a direct stimulatory action on the promoter and further that this Is mediated by the AP-1 transcription factor. In addition, we show that there are two separate cls-actlng sites that bind AP-1 and both are required for maximal stimulation. We further show that in AP-1-deficient cells ectoplc expression of AP-1 stimulates synthetic promoters containing two copies of each synthase element upstream of a minimal promoter. The physiological rationale of having both end product repression and direct activation by growth stimulatory cues is discussed.


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