ReviewThe molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis
Section snippets
Introduction β a historical perspective and nomenclature
Activating Transcription Factor (ATF) was first named in 1987 to refer to proteins that bind to the adenovirus early promoters E2, E3 and E4 at sites with a common core sequence βCGTCAβ (Lee et al., 1987). cAMP responsive element binding protein (CREB) was named in 1987 to refer to proteins that bind to the cAMP responsive element (CRE) on the somatostatin promoter (Montminy and Bilezsikjian, 1987). The consensus binding site for ATF was later defined as TGACGT(C/A)(G/A) (Lin and Green, 1988),
ATF3
ATF3 was originally isolated from a library derived from HeLa cells treated with tetradecanoylphorbol acetate (TPA) (Hai et al., 1989). Previously, we reviewed ATF3 and its potential roles in stress responses (Hai et al., 1999). Due to the space limit, we will briefly summarize the last review and discuss a few new findings since the last review.
Nomenclature, homologous proteins, and dimer formation of ATF4
A partial cDNA encoding the human ATF4 was isolated on the basis of its ability to bind to the consensus ATF/CRE site (Hai et al., 1989). Subsequently, full-length cDNA clones encoding identical or homologous proteins were isolated by a variety of methods. These include the human clones TAXCREB 67 (Tsujimoto et al., 1991) and CREB-2 (Karpinski et al., 1992), and the mouse clones mATF4 (Mielnicki and Pruitt, 1991, mapped to mouse chromosome 15, see Mielnicki et al., 1993), mTR67 (Chevray and
Nomenclature, homologous proteins, and dimer formation of ATF6
A partial cDNA encoding the human ATF6 was isolated on the basis of its ability to bind to the consensus ATF/CRE site (Hai et al., 1989). A human clone with significant similarity to ATF6 was isolated in an attempt to identify genes located in the HLA complex (Min et al., 1995). It was originally named CREB-related protein (CRB-RP), because it shares a small degree of homology to CREB: at the Nβ² terminal region over a stretch of about 300 residues (from 83 to 375), it is 23% identical to CREB.
Conclusions and future perspectives
In conclusion, all three ATF proteins reviewed above (ATF3, ATF4 and ATF6) are modulated by extracellular signals (at the level of their expression or activity). These observations indicate that one common role for the ATF/CREB family of proteins is their involvement in homeostasis. Consistent with this notion, the CREB/CREM and CRE-BP1 (ATF2) subfamilies of proteins are also modulated by extracellular signals. CREB is expressed in most cell types, but the protein is phosphorylated after
Acknowledgements
This study was supported by NIEHS08690, Central Ohio Cancer Research, the Central Ohio Diabetes Association, and the American Diabetes Association (to T.H.).
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