The Zinc Finger Transcription Factor Zif268/Egr-1 Is Essential for Schwann Cell Expression of the p75 NGF Receptor

Nikam, Savita; Tennekoon, Gihan; Christy, Barbara A.; Yoshino, Jun; Rutkowski, J. Lynn

doi:10.1006/mcne.1995.1026

Cited by 43 publications

(38 citation statements)

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“…Previous studies have shown that Egr-1 is required for the expression of p75 NTR [29], whereas Hipk2 can act as a repressor of TrkA transcription [46]. Therefore, when taken together, the above results in wild-type, caloric restricted, and p44 +/+ mice, and in SH-SY5Y cells are consistent with the possible involvement of Egr-1 and Hipk2 in the age-associated transcriptional regulation of p75 NTR and TrkA.…”

Section: Egr-1 and Hipk2 Are Required Elements For The Trka To P75 Ntsupporting

confidence: 86%

“…Among the many transcription factors that have been shown to regulate the expression of p75 NTR or TrkA, Egr-1, Hipk2, and Brn-3a are known to be continuously expressed during adulthood [1,5,28,29,36,42]. Our previous studies indicate that the expression levels of p75 NTR and TrkA are affected by normal aging; they also indicate that the effects of aging are blocked/delayed by caloric restriction and accelerated/aggravated by the p44 transgene in p44 +/+ animals [7,8].…”

Section: Egr-1 and Hipk2 Are Required Elements For The Trka To P75 Ntmentioning

confidence: 99%

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Egr-1 and Hipk2 are required for the TrkA to p75NTR switch that occurs downstream of IGF1-R

Costantini

Scrable

et al. 2009

Neurobiology of Aging

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The aging program mediated by IGF1-R is responsible for a naturally occurring TrkA-to-p75 NTR switch that leads to activation of the second messenger ceramide and increased production of the Alzheimer's disease amyloid β-peptide. Biochemical and genetic approaches that target IGF1-R signaling, p75 NTR , or ceramide are able to block the above events. Here, we show that the transcription factors Egr-1 and Hipk2 are required elements for the TrkA-to-p75 NTR switch downstream of IGF1-R signaling. Specifically, Egr-1 is required for the upregulation of p75 NTR , whereas Hipk2 is required for the downregulation of TrkA. In fact, gene silencing of Egr-1 abolished the ability of IGF1 to upregulate p75 NTR , whereas similar approaches directed against Hipk2 blocked the downregulation of TrkA. In addition, IGF1 treatment favored binding of Egr-1 and Hipk2 to the promoter of p75 NTR and TrkA, respectively. Finally, the expression levels of both Egr-1 and Hipk2 are upregulated in an age-dependent fashion. Such an event is opposed by caloric restriction, a model of delayed aging, and favored by the p44 transgene in p44 +/+ animals, a model of accelerated aging.

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Section: Egr-1 and Hipk2 Are Required Elements For The Trka To P75 Ntsupporting

confidence: 86%

Section: Egr-1 and Hipk2 Are Required Elements For The Trka To P75 Ntmentioning

confidence: 99%

Egr-1 and Hipk2 are required for the TrkA to p75NTR switch that occurs downstream of IGF1-R

Costantini

Scrable

et al. 2009

Neurobiology of Aging

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“…Egr-2 recognizes EGR response elements in promotor regions of a number of neuronal genes that are likely to play a role in mediating plastic changes that occur in response to cognitive demand. These genes encode, for example, the synaptic vesicle proteins synapsin I and II (Thiel et al, 1994;Petersohn et al, 1995), synaptobrevin 2 , and synaptophysin (Özçelik et al, 1990) that are involved in regulating neurotransmitter release, the nerve growth factor receptor p75 (Nikam et al, 1995), and the enzyme acetylcholinesterase (Li et al, 1993) that degrades a neurotransmitter essential for the orienting control function of attention (Witte et al, 1997). Thus, future studies must not only identify the types of neurons that exhibit induced egr-2 expression in response to ASST exposure, but also identify the individual downstream genes that are activated (or even repressed; O'Donovan et al, 1999) by egr-2 expression in the OFC and mPFC.…”

Section: Discussionmentioning

confidence: 99%

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

DeSteno

Schmauss

2008

Neuroscience

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Early growth response (egr) genes encode transcription factors that are induced by stimuli that cause synaptic plasticity. Here we show that the expression of one member of this family, egr-2, is induced in the orbital frontal cortex (OFC) and medial prefrontal cortex (mPFC) of mice performing an attention-set-shifting task (ASST). The ASST is a series of two-choice perceptual discriminations between different odors and textures. Within the OFC and mPFC, different subregions exhibited egr-2 induction in response to different test-related features. In the medial OFC and the anterior cingulate subregion of the mPFC, egr-2 induction occurred in response to exposure to the novel odor stimulus. In the ventrolateral OFC and the pre-and infralimbic mPFC, additional egr-2 induction occurred during the associative learning phase of the ASST. In the infralimbic mPFC, further egr-2 induction occurred when mice performed set-shifting and reversal learning phases of the ASST. Mice with enhanced set-shifting performance exhibited decreased egr-2 induction in the mPFC indicating that the magnitude of egr-2 induction correlates with the magnitude of attentional demand. This decrease was largest in the infralimbic mPFC suggesting further that egr-2 induction in this region plays a role in the attentional control during set-shifting.In contrast to egr-2, neither egr-1 nor egr-3 expression was altered in ASST-tested mice, and no egr-2 induction occurred in mice that performed a spatial working memory task. These findings suggest a specific role of egr-2-mediated transcriptional activation in cognitive functions associated with attention. Keywordsearly growth response gene; medial prefrontal cortex; orbital frontal cortex; attention; working memory; miceThe earliest genomic response to synaptic activity is the induction of expression of immediate early genes (IEGs) encoding transcription factors that participate in synaptic and structural neuronal responses to external stimulation. Although induction of expression of the IEG c- ., Email address: cs581@columbia.edu (C. Schmauss). Section Editor: Dr. Werner Sieghart (Molecular Neuroscience) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 April 21. Published in final edited form as:Neuroscience. 2008 March 18; 152(2): 417-428. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptfos is a powerful tool to map the activation of neuronal pathways (Sagar et al, 1988), the identification of other IEG transcription factors is critical...

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“…Individually, both Krox-24 and Egr-3 directly activate p75NTR in cultured Schwann cells, and in vivo loss of either gene alone fails to increase expression of the other. This indicates that in injured nerves Krox-24 or Egr-3 alone can activate p75NTR expression in the absence of the other (Gao et al, 2007;Nikam et al, 1995). p75NTR, which is known to be expressed by immature Schwann cells, is suppressed in myelinating Schwann cells but reactivated in injured nerves Taniuchi et al, 1988).…”

Section: Krox-24 and Egr-3mentioning

confidence: 95%

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Jessen

Mirsky

2008

Glia

453

409

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Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury and demyelinating neuropathies. We review recent evidence that this dedifferentiation depends on activation of specific intracellular signaling molecules that drive the dedifferentiation program. In particular, we discuss the idea that Schwann cells contain negative transcriptional regulators of myelination that functionally complement positive regulators such as Krox-20, and that myelination is therefore determined by a balance between two opposing transcriptional programs. Negative transcriptional regulators should be expressed prior to myelination, downregulated as myelination starts but reactivated as Schwann cells dedifferentiate following injury. The clearest evidence for a factor that works in this way relates to c-Jun, while other factors may include Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular-related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating cells is also discussed. We also review evidence that neurotrophin 3 (NT3), purinergic signaling, and nitric oxide synthase are involved in suppressing myelination. The realization that myelination is subject to negative as well as positive controls contributes significantly to the understanding of Schwann cell plasticity. Negative regulators are likely to have a major role during injury, because they promote the transformation of damaged nerves to an environment that fosters neuronal survival and axonal regrowth. In neuropathies, however, activation of these pathways is likely to be harmful because they may be key contributors to demyelination, a situation which would open new routes for clinical intervention. V V C 2008 Wiley-Liss, Inc.

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The Zinc Finger Transcription Factor Zif268/Egr-1 Is Essential for Schwann Cell Expression of the p75 NGF Receptor

Cited by 43 publications

References 0 publications

Egr-1 and Hipk2 are required for the TrkA to p75NTR switch that occurs downstream of IGF1-R

Egr-1 and Hipk2 are required for the TrkA to p75NTR switch that occurs downstream of IGF1-R

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

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