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The cAMP response element-binding protein (CREB) was identified almost 20 years ago. Since then, CREB has become one of the most extensively studied tran-scription factors. Currently, the importance of CREB for numerous physiological events has been confirmed by the number of targets: up to 4000 genes or up to 6000 loci. | IFEBS Journal MINIREVIEW SERIES Transcription factor cAMP response element-binding protein CREB Hiroshi Takemori Laboratory of CellSignaling and Metabolism National institute of BiomedicalInnovation Osaka Japan The cAMP response element-binding protein CREB was identified almost 20 years ago. Since then CREB has become one of the most extensively studied transcription factors. Currently the importance of CREB for numerous physiological events has been confirmed by the number of targets up to 4000 genes or up to 6000 loci. In addition it is well known that numerous signals not only the cAMP signal but also Ca2 cellular stresses and cell cycle systems regulate CREB activity in a phosphorylation-dependent manner. In mice knockout models targeting CREB and its cognate factors have disclosed essential functions of the CREB family in cell survival from early embryo to germ cells. By contrast the CREB family factors are found only in multicellular animals although cAMP- stress-dependent gene regulation plays an important role in a variety of organisms such as Escherichia coli and yeast indicating that CREB may regulate physiological events acquired by animals during their evolution. In view of these findings we summarize a new insight of CREB regulation actualized through its basic leucine zipper domain and three physiological events regulated by CREB ischemia tumorigenesis and memory. Hiroshi Takemori Junko Kajimura and Mitsuhiro Okamoto describe transactivation activities encoded by the basic leucine zipper bZIP domain. Studies of protein-protein interaction suggest the presence of CREB s transactivation activities outside of its transactivation domain. This notion was confirmed by the discovery of the CREB specific coactivator transducer of regulated CREB activity TORC . TORCs are also regulated by phosphorylation but they are active in their dephos-pho-forms. The dephosphorylation of TORCs occurs concomitantly with the phosphorylation of CREB. The combination of .
