Differential regulation of three members of the ATF/CREB family of DNA-binding proteins.
The ATF/CRE binding site can mediate transcriptional activation by cAMP, the adenovirus E1A protein and the human T-cell leukaemia virus 1 (HTLV1) tax protein. A large number of different proteins bind specifically to this element either as homodimers or as heterodimers. Using GAL4-ATF/CREB fusions, we have investigated the regulatory functions of three members of this family. CREB1 (CREB) is strongly activated by cAMP and weakly activated by the E1A protein. In contrast, CREB2 (CRE-BP1, ATF2) is strongly activated by E1A but is insensitive to cAMP stimulation. ATF1 is weakly activated by cAMP but is not activated by E1A. All three proteins are insensitive to activation by the HTLV1 tax protein. The N-terminal region of CREB2, from amino acid residues 19 to 112, is both necessary and sufficient for E1A activation. This region contains a putative C2H2 metal-binding finger, and single amino acid substitutions of the cysteine residues severely decreased CREB2 activity. In contrast, mutations affecting a potential protein kinase A and casein kinase II phosphorylation site within this region had little effect.
Flint
K J
KJ
Gene Regulation Laboratory, Imperial Cancer Research Fund, London, UK.
Jones
N C
NC
D051696:Activating Transcription Factors; D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae / Q000235:genetics*; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005656:Fungal Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D016356:Gene Products, tax / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009856:Oncogene Proteins, Viral / Q000502:physiology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D051696:Activating Transcription Factors; D017456:Adenovirus Early Proteins; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D016356:Gene Products, tax; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000242:Cyclic AMP