title: Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element.
abstract: The cAMP response element (CRE) is an octanucleotide motif (TGACGTCA) that mediates diverse transcriptional regulatory effects. In this report we describe the isolation and characterization of a full-length cDNA that encodes a CRE binding protein called CREB-2. Like other ATF/CREB transcription factors, the 351-amino acid CREB-2 protein contains a COOH-terminal leucine-zipper motif and an adjacent basic domain. CREB-2 mRNA is expressed ubiquitously in human tumor cell lines and mouse organs suggesting that it is involved in regulating transcription in a wide variety of cell types. Overexpression of CREB-2 resulted in a consistent and significant repression of CRE-dependent transcription in CV-1 cells. Deletional analyses localized the transcriptional repressor activity of CREB-2 to a 102-amino acid COOH-terminal region (amino acids 249-351) that contains the leucine-zipper and basic domains of the molecule. These results demonstrate that CRE-dependent transcription can be both positively and negatively regulated by structurally related members of the ATF/CREB family.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109.
authors.forename: B A
authors.initials: BA
authors.lastname: Karpinski
authors.forename: G D
authors.initials: GD
authors.lastname: Morle
authors.forename: J
authors.initials: J
authors.lastname: Huggenvik
authors.forename: M D
authors.initials: MD
authors.lastname: Uhler
authors.forename: J M
authors.initials: JM
authors.lastname: Leiden
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011953:Receptors, Cyclic AMP; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011953:Receptors, Cyclic AMP; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases; D011493:Protein Kinase C