The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth

Béata Töröcsik, James M Angelastro, Lloyd A. Greene

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We used serial analysis of gene expression to identify new NGF-responsive immediate early genes (IEGs) with potential roles in neuronal differentiation. Among those identified was MafK, a small Maf family basic region and leucine zipper transcriptional repressor and coactivator expressed in immature neurons. NGF treatment elevates the levels of both MafK transcripts and protein. In contrast, there is no effect on expression of the closely related MafG. Unlike many other NGF-responsive IEGs, MafK regulation shows selectivity and is unresponsive to epidermal growth factor, depolarization, or cAMP derivatives. Inhibitor studies indicate that NGF-promoted MafK regulation is mediated by an atypical isoform of PKC but not by mitogen-activated kinase kinase, phospholipase Cγ, or phosphoinositide 3′-kinase. Interference with MafK expression or activity by small interfering RNA and dominant negative strategies, respectively, suppresses NGF-promoted outgrowth and maintenance of neurites by PC12 cells and neurite outgrowth by immature telencephalic neurons. Our findings support a role for MafK as a novel regulator of neuronal differentiation.

Original languageEnglish (US)
Pages (from-to)8971-8980
Number of pages10
JournalJournal of Neuroscience
Volume22
Issue number20
StatePublished - Oct 15 2002
Externally publishedYes

Keywords

  • Differentiation
  • Immediate early gene
  • MafK
  • NGF
  • PC12 cell
  • Transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)

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