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 language | English (US) |
|---|---|
| Pages (from-to) | 8971-8980 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience |
| Volume | 22 |
| Issue number | 20 |
| State | Published - Oct 15 2002 |
| Externally published | Yes |
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Keywords
- Differentiation
- Immediate early gene
- MafK
- NGF
- PC12 cell
- Transcription factor
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth. / Töröcsik, Béata; Angelastro, James M; Greene, Lloyd A.
In: Journal of Neuroscience, Vol. 22, No. 20, 15.10.2002, p. 8971-8980.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth
AU - Töröcsik, Béata
AU - Angelastro, James M
AU - Greene, Lloyd A.
PY - 2002/10/15
Y1 - 2002/10/15
N2 - 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.
AB - 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.
KW - Differentiation
KW - Immediate early gene
KW - MafK
KW - NGF
KW - PC12 cell
KW - Transcription factor
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M3 - Article
C2 - 12388604
AN - SCOPUS:0037109676
VL - 22
SP - 8971
EP - 8980
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 20
ER -