Scientists observed that CREB activates specific genes based on the co-factor involved.

Investigators at St. Jude Children’s Research Hospital discovered how a transcription factor called CREB triggers gene activity that might cause effects ranging from learning and memory capabilities to glucose production in the liver.

The St. Jude team showed that each gene that responds to the protein CREB chooses which co-factors CREB uses to activate that gene. This finding adds further insight into the mechanism of how cells use CREB to activate specific genes in response to cAMP, which acts as a messenger for a variety of stimuli, including hormones and neurotransmitters.

It also suggests that the current model scientists use to explain how CREB works is too simple, says Paul Brindle, Ph.D., associate member of the department of biochemistry at St. Jude and senior author of a report on this work that appears in the June 20 issue of The EMBO Journal.

“This more complex view of how CREB works may help us understand how this single transcription factor can stimulate many different genes, depending on which tissues are using it and which signaling molecule caused cAMP to put CREB to work,” Dr. Brindle says. “A drug that blocked the specific co-factors CREB needs in the liver to trigger activity of genes that make glucose could reduce blood levels of this sugar in people with diabetes, but at the same time, CREB could continue its other jobs without interruption.”

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