Abstract
Activating transcription factor 3 (ATF3) belongs to the ATF/cyclic AMP responsive element binding family of transcription factors and is often described as an adaptive response gene whose activity is usually regulated by stressful stimuli. Although expressed in a number of splice variants and generally recognized as a transcriptional repressor, ATF3 has the ability to interact with a number of other transcription factors including c-Jun to form complexes which not only repress, but can also activate various genes. ATF3 expression is modulated mainly at the transcriptional level and has markedly different effects in different types of cell. The levels of ATF3 mRNA and protein are normally very low in neurons and glia but their expression is rapidly upregulated in response to injury. ATF3 expression in neurons is closely linked to their survival and the regeneration of their axons following axotomy, and that in peripheral nerves correlates with the generation of a Schwann cell phenotype that is conducive to axonal regeneration. ATF3 is also induced by Toll-like receptor (TLR) ligands but acts as a negative regulator of TLR signaling, suppressing the innate immune response which is involved in immuno-surveillance and can enhance or reduce the survival of injured neurons and promote the regeneration of their axons.
Highlights
MOLECULAR NEUROSCIENCEReviewed by: Hiroshi Kiyama, Nagoya University, Japan Simone Di Giovanni, University of Tuebingen, Germany
It has long been known that the ability of peripheral axons to regenerate is fundamentally greater than that of axons in the brain, spinal cord, or optic nerves
activating transcription factor 3 (ATF3), and several other growth-associated molecules including GAP43, were not upregulated by corticospinal neurons after spinal cord injury but they were upregulated after intracortical axotomy (Mason et al, 2003). Together these results suggest that ATF3 is upregulated by thalamic projection neurons and by neocortical projection neurons following axotomy, but only if the injury is sufficiently proximal to the cell body
Summary
Reviewed by: Hiroshi Kiyama, Nagoya University, Japan Simone Di Giovanni, University of Tuebingen, Germany. Expressed in a number of splice variants and generally recognized as a transcriptional repressor, ATF3 has the ability to interact with a number of other transcription factors including c-Jun to form complexes which repress, but can activate various genes. ATF3 expression is modulated mainly at the transcriptional level and has markedly different effects in different types of cell. The levels of ATF3 mRNA and protein are normally very low in neurons and glia but their expression is rapidly upregulated in response to injury. ATF3 expression in neurons is closely linked to their survival and the regeneration of their axons following axotomy, and that in peripheral nerves correlates with the generation of a Schwann cell phenotype that is conducive to axonal regeneration. ATF3 is induced by Toll-like receptor (TLR) ligands but acts as a negative regulator of TLR signaling, suppressing the innate immune response which is involved in immuno-surveillance and can enhance or reduce the survival of injured neurons and promote the regeneration of their axons
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