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) resp onsive gene products expressed in PC12 cells. In previous work, we ide ntified 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 iden tify a transcription factor that specifically recognizes this regulato ry 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 I REBF1 augments NGF-responsive ST-1 gene regulation, but does not affec t basal levels of expression. On the other hand, expression of a mutat ed form of this transcription factor lacking the DNA binding domain at tenuated NGF responsiveness, without affecting basal levels of express ion. These data suggest that IREBF1 is part of the NGF-responsive tran scriptional machinery necessary for the expression of ST-1 in PC12 cel ls.