Analysis of Signal-Dependent Gene Expression by Proteins of the CREB family | © dkfz.de

Whereas steroid hormones have their receptors within the cell, growth factors and polypeptide hormones control gene activity via intracellular signal transduction pathways to the nucleus often involving protein phosphorylation, which results also in phosphorylation of the proteins of the CREB family, CREB, CREM, and ATF1. These transcription factors contain a bZIP DNA binding domain and function as homo- or heterodimers. To define their function in signal-dependent gene expression in vivo we have generated mouse mutants which led to selective inactivation of the genes for these three members of the CREB family. Since animals without CREB die shortly after birth we have generated tissue-specific mutations. Ablation of CREB and CREM in the developing central nervous system leads to extensive apoptosis. If we inactivate the CREB gene once development is completed we see, however, progressive neuronal degeneration in restricted regions of the hippocampus and parts of the striatum. These results indicate an important role of CREB proteins in the regulation of neuronal survival.