title: cAMP activation of CAAT enhancer-binding protein-beta gene expression and promoter I of acetyl-CoA carboxylase.
abstract: The acetyl-CoA carboxylase (ACC) gene contains two distinct promoters, denoted PI and PII. PI is responsible for the generation of class I ACC mRNAs which are induced in a tissue-specific manner under lipogenic conditions. PII generates class II ACC mRNAs which are expressed constitutively. During 30A5 preadipocyte differentiation, both promoters are activated; the preadipocytes must be pretreated with cAMP for this activation to occur. In this report, we present evidence that CAAT enhancer-binding protein-beta (C/EBP-beta) is induced and involved in the PI activation by cAMP. Expression of the reporter gene under the control of the PI promoter is activated within 3 h after treatment of 30A5 cells with a cyclic AMP analogue, 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine, in association with the accumulation of C/EBP-beta mRNA and protein. These accumulations were inhibited in the presence of H8, a protein kinase inhibitor; H8 also inhibited activation of PI by cAMP. However, the induction of reporter gene expression and the increase of C/EBP-beta mRNA by cAMP were not affected by treatment with tumor necrosis factor alpha, which completely inhibited the accumulation of C/EBP-alpha mRNA. Overexpression of C/EBP-beta by transfection with the C/EBP-beta gene led to increased binding of C/EBP-beta to DNA and partial PI activation. cAMP did not affect the amount of C/EBP-beta binding to the DNA but did promote phosphorylation of C/EBP-beta and PI activation. As in the case of C/EBP-alpha, C/EBP-beta bound to the CCAAT box of the PI promoter. These results indicate that cAMP not only induces, but also activates, bound C/EBP-beta through phosphorylation for PI activation. Our studies also indicate that cAMP induces C/EBP-alpha. C/EBP-beta induction, however, precedes that of C/EBP-alpha.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Tae
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis* / Q000235:genetics*; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D016385:TATA Box; D013873:Thionucleotides / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D000103:Acetyl-CoA Carboxylase; D015056:1-Methyl-3-isobutylxanthine