Pre‐Metazoan Ancestry of CREB as a Kinase‐Inducible Transcription Factor

Abstract

The cyclic AMP response element binding protein (CREB) is a bZIP transcription factor activated by phosphorylation within its kinase‐inducible domain (KID), which is mediated by PKA and other kinases. CREB activation promotes the expression of genes regulating cell proliferation and cell survival, and CREB activation in neurons plays an essential role in memory formation. Herein, we have investigated the evolution of CREB in metazoan and unicellular opisthokont lineages. We identified CREB homologs with conserved bZIP domains and KID‐homologous phosphoacceptor domains in basal metazoans including cnidarians, ctenophores, placozoans, and sponges as well as choanoflagellates, the closest unicellular relatives of metazoans. The metazoan and choanoflagellate CREB homologs also possessed conserved residues known to be required for the formation of CREB‐coactivator complexes. This report therefore establishes the pre‐metazoan ancestry of CREB as a kinase‐inducible transcriptional regulator.