A CONSENSUS INSULIN-RESPONSE ELEMENT IS ACTIVATED BY AN ETS-RELATED TRANSCRIPTION FACTOR

Insulin increases expression of somatostatin-chloramphenicol acetyltra nsferase (CAT) constructs 10-fold and thymidine kinase-CAT constructs 5-fold in GH4 cells. These responses are similar to our previously rep orted data on insulin-increased prolactin-CAT expression, They are als o observed in HeLa cells and are thus not cell type specific, The evid ence suggests that the insulin responsiveness of these genes is mediat ed by an Ets-related transcription factor, First, linker-scanning muta tions and/or deletions of the prolactin, somatostatin, and thymidine k inase promoters suggest that their insulin responsiveness is mediated by the sequence CGGA, This sequence is identical with the response ele ment of the Ets-related transcription factors, Second, CGGA-containing sequences placed at -88 in the Delta MTV-CAT reporter plasmid conferr ed insulin responsiveness to the mammary tumor virus promoter, Third, expression of the DNA-binding domain of c-Ets-a, which acts by blockin g effects mediated by Ets-related transcription factors, inhibits the response of these promoters to insulin, Finally, the Ets-related prote ins Sap and Elk-l bind to the prolactin, somatostatin, and thymidine k inase insulin response elements, An Ets-like element was found in all insulin-sensitive promoters examined and may serve a similar function in those promoters.