CREB (cAMP response element-binding) proteins are transcription factors which bind to certain sequences called cAMP response elements (CRE) in DNA and thereby increase or decrease the transcription of certain genes. CREB is highly related (in structure and function) to CREM (cAMP response element modulator) and ATF-1 (activating transcription factor-1) proteins. CREB proteins are active in many animals, including humans.

The typical (somewhat simplified) sequence of events is as follows: a signal arrives at the cell surface, activates the corresponding receptor, which leads to the production of a second messenger such as cAMP or Ca2 , which in turn activates a protein kinase. This protein kinase moves to the cell nucleus, where it activates a CREB protein.