Transcriptional activation function of zinc finger protein TIS11 and its negative regulation by phorbol ester.
TIS11, a CCCH zinc finger protein, is one of the typical growth factor-inducible nuclear proteins. We found that TIS11 possesses the potential to activate transcription when fused to the GAL4 DNA binding domain and transiently cotransfected into rat pheochromocytoma PC12 cells along with a GAL4-responsive luciferase reporter gene. The study with deletion mutants of TIS11 revealed that the major transactivation region is located at the N-terminal 101 amino acid residues and that the remaining central and C-terminal region had a moderate transactivational activity. In addition, the transactivational activity of TIS11 was found to be significantly reduced by treating the transfectants with phorbol 12-myristate 13-acetate (PMA). PMA-induced inactivation of TIS11 was blocked by calphostin C, a protein kinase C inhibitor, and PD98059, a mitogen-activated protein (MAP) kinase kinase inhibitor. These results suggested that TIS11 functions as a positive transcriptional regulator and that the protein kinase C/MAP kinase signaling cascade is involved in negative regulation of TIS11 by PMA.
Department of Analytical Neurobiology, Meijo University, Tempaku, Nagoya, 468-8503, Japan.
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Murata
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Hikita
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Kaneda
D017501:Adenovirus E1B Proteins / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics; D017930:Genes, Reporter / Q000187:drug effects; D017874:Immediate-Early Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D016297:Mutagenesis, Site-Directed; D016716:PC12 Cells; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D051816:Tristetraprolin; D016335:Zinc Fingers / Q000235:genetics*
D017501:Adenovirus E1B Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D017874:Immediate-Early Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D051816:Tristetraprolin; C497554:Zfp36 protein, rat; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D013755:Tetradecanoylphorbol Acetate