Role of the bZIP transcription factor IREBF1 in the NGF induction of stromelysin-1 (transin) gene expression in PC12...

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.