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Cyclic AMP, the Cyclic AMP Receptor Protein, and Their Dual Control of the Galactose Operon

Benoit De Crombrugghe, Ira Pastan


In this paper we summarize the experimental evidence which led to the demonstration of the role of cyclic AMP and its receptor protein (CRP) in the activation of gene transcription in bacteria. We also examine the function of this protein in the control of the galactose operon of Escherichia coli. Regulation of this operon is more complex than that of the lac operon: two interspersed promoters which respond to different regulatory mechanisms control the expression of the gal genes. The activity of one gal promoter is stimulated and the activity of the other gal promoter is inhibited by cyclic AMP and CRP.

When E. coli find both glucose and lactose in their environment, they metabolize glucose and repress the utilization of lactose. This phenomenon has been called “catabolite or glucose repression of lactose utilization,” and it results in the inhibition of the synthesis of the enzymes for lactose metabolism (Monod 1947; Magasanik 1962). This repression by glucose is not unique for the lactose metabolizing enzymes and has been observed for the enzymes which degrade a number of other carbohydrates (Epps and Gale 1942; Magasanik 1962; Koch et al. 1964). One intracellular compound which varies when the composition of the medium changes is the cyclic nucleotide adenosine-3′,5′-monophosphate (cyclic AMP). Sutherland and his colleagues, who had first discovered cyclic AMP in animal cells, found that when E. coli were growing in a glucose-containing medium they had low levels of cyclic AMP and that withdrawal of glucose...

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