The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis

The mammalian ATF/CREB family of transcription factors represents a large g roup of basic region-leucine zipper (bZip) proteins which was originally de fined in the late 1980s by their ability to bind to the consensus ATF/CRE s ite 'TGACGTCA'. Over the past decade, cDNA clones encoding identical or hom ologous proteins have been isolated by different laboratories and given dif ferent names. These proteins can be grouped into subgroups according to the ir amino acid similarity. In this review, we will briefly describe the clas sification of these proteins with a historical perspective of their nomencl ature. We will then review three members of the ATF/CREB family of proteins : ATF3, ATF4 and ATF6. We will address four issues for each protein: (a) ho mologous proteins and alternative names, (b) dimer formation with other bZi p proteins. (c) transcriptional activity, and (d) potential physiological f unctions. Although the name Activating Transcription Factor (ATF) implies t hat they are transcriptional activators, some of these proteins are transcr iptional repressors. ATF3 homodimer is a transcriptional repressor and ATF4 has been reported to be either an activator or a repressor. We will review the reports on the transcriptional activities of ATF4. and propose potenti al explanations for the discrepancy, Although the physiological functions o f these proteins are not well understood. some clues can be gained from stu dies with different approaches. When the data are available, we will addres s the following questions. (a) How is the expression (at the mRNA level or protein level) regulated? (b) How are the transcriptional activities regula ted'? (c) What are the interacting proteins (other than bZip partners)? (d) What are the consequences of ectopically expressing the gene (gain-of-func tion) or deleting the gene (loss-of-function)? Although answers to these qu estions are far from being complete, together they provide clues to the fun ctions of these ATF proteins. Despite the diversity in the potential functi ons of these proteins, one common theme is their involvement in cellular re sponses to extracellular signals. indicating a role for these ATF proteins in homeostasis. (C) 2001 Published by Elsevier Science B.V. All rights rese rved.