The cyclic AMP response element (CRE)-binding protein (CREB) is probably one of the best understood phosphorylation dependent transcription factors. Increases in the concentration of either calcium or cAMP can induce activation of CREB, which leads to the transcription of target genes with cAMP responsive elements in their promoters. They regulate a wide range of biological functions, such as growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms and memory.
Cells will undergo genotypic changes resulting in reduced responsiveness over time in normal cell culture conditions. Genetic instability is a biological phenomenon that occurs in all stably transfected cells. Therefore, it is critical to prepare an adequate number of frozen stocks at early passages.