Regulation of trans-activating capacity of CRE-BPa by phorbol ester tumor promoter TPA.
CRE-BPa, here designated as CRE-BPa alpha, is a novel member of the CRE (cAMP response element)-binding protein CRE-BP1 family. CRE-BPa alpha has four regions highly homologous to CRE-BP1, including a putative metal finger structure and a DNA-binding domain consisting of a basic amino acid cluster and a leucine zipper. CRE-BPa specifically binds to CRE as a homodimer or heterodimer with c-Jun or CRE-BP1. Here we report three alternative splicing forms of CRE-BPa alpha: two of them, CRE-BPa beta and CRE-BPa gamma, lack the N-terminal 7 and 33 amino acids of CRE-BPa alpha, and the third one CRE-BPa delta, has 16 additional amino acids in the N-terminus and amino acids 156-508 of CRE-BPa alpha. In CAT cotransfection experiments using CV-1 cells, transient expression of each of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE-dependent transcription, respectively. Interestingly, these weak trans-activating capacities of CRE-BPa proteins were enhanced 2.7- to 3.6-fold by treatment of cells with 12-O-tetradecanoyl-phorbol 13-acetate (TPA). However, CRE-BPa did not affect the TPA-induced and TRE (TPA response element)-dependent transcription. These results indicate that CRE-BPa is a CRE-dependent trans-activator, and that CRE-BPa can confer TPA inducibility on CRE. Thus, CRE-BPa has an unique characteristic of cross-talk between cAMP pathway and TPA pathway.
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Laboratory of Molecular Genetics, Tsukuba Life Science Center, Ibaraki, Japan.
Maekawa
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Nomura
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Nakata
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Ishii
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D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000187:drug effects; D051699:Cyclic AMP Response Element-Binding Protein A; D004247:DNA / Q000737:chemistry*; D007668:Kidney; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection
D051698:Activating Transcription Factor 2; C497102:CREB5 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D051699:Cyclic AMP Response Element-Binding Protein A; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate