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The Journal of Neuroscience, October 15, 2002, 22(20):8971-8980
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, and
Lloyd A.
Greene
Department of Pathology and Center for Neurobiology and Behavior,
Columbia University College of Physicians and Surgeons, New York, New
York 10032
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 C , 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.
Key words:
MafK; NGF; immediate early gene; transcription factor; differentiation; PC12 cell
Copyright © 2002 Society for Neuroscience 0270-6474/02/22208971-10$05.00/0
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