Role of the bZIP transcription factor IREBF1 in the NGF induction of stromelysin-1 (transin) gene expression in PC12 cells.
Stromelysin-1 (ST-1) is one of the most nerve growth factor-(NGF) responsive gene products expressed in PC12 cells. In previous work, we identified a novel NGF-responsive element in the proximal promoter region of the ST-1 gene that participates in this induction, and showed that it bound a protein present in the nuclei of PC12 cells. Here, we identify a transcription factor that specifically recognizes this regulatory element-the interferon-response element binding factor-1 (IREBF1), a member of the basic leucine zipper gene family. We show that IREBF1 is constitutively expressed in PC12 cells and that overexpression of IREBF1 augments NGF-responsive ST-1 gene regulation, but does not affect basal levels of expression. On the other hand, expression of a mutated form of this transcription factor lacking the DNA binding domain attenuated NGF responsiveness, without affecting basal levels of expression. These data suggest that IREBF1 is part of the NGF-responsive transcriptional machinery necessary for the expression of ST-1 in PC12 cells.
deSouza
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Department of Cell & Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
Nordstrom
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Ciment
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D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D016350:Leucine Zippers; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics*; D009414:Nerve Growth Factors / Q000502:physiology*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D009414:Nerve Growth Factors; D010750:Phosphoproteins; D014157:Transcription Factors; D004247:DNA; D019278:Matrix Metalloproteinase 3