The ATF Transcription Factors in Cellular Adaptive Responses

The mammalian ATF/CREB family of transcription factors represents a group of basic region-leucine zipper (bZip) proteins consisted of almost 20 members. The name ATF or CREB was originally defined in the late 1980’s by their ability to bind to the consensus ATF/CRE site “TGACGTCA.” Over the years, cDNA clones encoding identical or homologous proteins have been isolated. Dendrogram analysis of these proteins on the basis of their amino acid sequences in the bZip region indicates that some of them are more similar to the other bZip proteins-AP-1 (Fos/Jun) and C/EBP — than to the other ATF/CREB proteins. Furthermore, members of the ATF/CREB proteins form heterodimers with the AP-1 or C/EBP proteins and the resulting dimers have altered DNA binding specificity. Therefore, the ATF prefix of these bZip proteins reflects the history of discovery, rather than the real similarity between them. In this chapter, I will briefly describe the classification of the ATF/CREB proteins with a historical perspective of their nomenclature, and then briefly review three ATF proteins — ATF3, ATF4 and ATF6. One common feature of these proteins is their involvement in cellular responses to extracellular signals, suggesting a role for these ATF proteins in adaptation and homeostasis.