ATF3 enhances c-Jun-mediated neurite sprouting.
The AP-1 transcription factor c-Jun is induced in axotomized neurons of the peripheral and central nervous systems, and in both cases upregulation of c-Jun expression has been correlated with axonal regeneration. More recently there has been interest in the c-Jun-related bZIP transcription factor, ATF3, and its function in neurons. ATF3 is also induced in nerve cells in response to axotomy and there is a correlation between increased ATF3 expression and upregulation of c-Jun in surviving neurons. Moreover, c-Jun is able to induce expression of ATF3. We investigated the effect of co-expressing c-Jun and ATF3 in two neuronal-like cell lines to model transcriptional events occurring in axotomized neurons undergoing regeneration. We show that expression of ATF3 with c-Jun significantly enhances c-Jun-mediated neurite sprouting, and that this phenotype is most likely mediated by a physical association of these two transcription factors. Our results suggest that a program of axonal regeneration is initiated when both c-Jun and ATF3 are upregulated in neurons in response to axotomy.
Pearson
Andree G
AG
Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Gray
Carol W
CW
Pearson
John F
JF
Greenwood
Jeffrey M
JM
During
Matthew J
MJ
Dragunow
Michael
M
D051700:Activating Transcription Factor 3; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D045744:Cell Line, Tumor; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011233:Precipitin Tests / Q000379:methods; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014404:Tubulin / Q000378:metabolism
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D014404:Tubulin