title: The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1.
abstract: Binding of the human transcription factor Jun/AP-1 to a conserved 8 bp nucleotide sequence (TRE) is responsible for increased transcription of different cellular genes in response to tumor promoters, such as TPA, and serum factors. Enhanced Jun/AP-1 activity in TPA-stimulated cells is regulated by two different mechanisms: a posttranslational event acting on pre-existing Jun/AP-1 molecules, and transcriptional activation of jun gene expression leading to an increase in the total amount of Jun/AP-1. Induction of jun transcription in response to TPA is mediated by binding of Jun/AP-1 to a high-affinity AP-1 binding site in the jun promoter region. Site-specific mutagenesis of this binding site prevents TPA induction and trans-activation by Jun/AP-1. These results clearly demonstrate that jun transcription is directly stimulated by its own gene product. This positive regulatory loop is likely to be responsible for prolonging the transient signals generated by activation of protein kinase C.
mesh_terms: D002478:Cells, Cultured; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate