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Gene Review

Atf3  -  activating transcription factor 3

Rattus norvegicus

Synonyms: Activating transcription factor 3, Cyclic AMP-dependent transcription factor ATF-3, LRF-1, LRFI, Liver regeneration factor 1, ...
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Disease relevance of Atf3

  • Overexpression of ATF3 by adenovirus inhibits the mitogen-activated kinase kinase kinase 1 (MEKK1)-c-Jun N-Terminal Kinase (JNK)-induced apoptosis and induces neurite elongation via Akt activation in PC12 cells and superior nerve ganglion neurons [1].
  • This effect was not accompanied by changes in dorsal root ganglion (DRG) cell number, expression of activating transcription factor 3 (ATF3), or alterations in calcitonin gene related peptide (CGRP) or isolectin B4 binding; and was not mimicked by partial nerve damage [2].
  • ATF3-positive neurons in these animals were located in regions of the TRN and MGN containing retrogradely labeled neurons and the great majority were also labeled with DiAsp [3].
  • Biphasic expression of activating transcription factor-3 in neurons after cerebral infarction [4].
  • During progression, LRF-1 and ets-2 showed a 2- to 3-fold higher expression in persistent nodules and hepatocellular carcinomas than in the corresponding surrounding liver tissues, whereas the expression of the jun genes was 3- to 4-fold increased both in lesions and in surrounding livers when compared to age-matched control rats [5].

High impact information on Atf3


Biological context of Atf3


Anatomical context of Atf3


Associations of Atf3 with chemical compounds

  • During promotion in the RH-model, the mRNA expression of c-jun and LRF-1 was 2- to 8-fold elevated in both initiated and uninitiated rats receiving 2-AAF [5].

Physical interactions of Atf3

  • ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins [15].

Regulatory relationships of Atf3

  • Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury [1].

Other interactions of Atf3


Analytical, diagnostic and therapeutic context of Atf3


  1. Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation. Nakagomi, S., Suzuki, Y., Namikawa, K., Kiryu-Seo, S., Kiyama, H. J. Neurosci. (2003) [Pubmed]
  2. Neonatal inflammation and primary afferent terminal plasticity in the rat dorsal horn. Walker, S.M., Meredith-Middleton, J., Cooke-Yarborough, C., Fitzgerald, M. Pain (2003) [Pubmed]
  3. Upregulation of activating transcription factor 3 (ATF3) by intrinsic CNS neurons regenerating axons into peripheral nerve grafts. Campbell, G., Hutchins, K., Winterbottom, J., Grenningloh, G., Lieberman, A.R., Anderson, P.N. Exp. Neurol. (2005) [Pubmed]
  4. Biphasic expression of activating transcription factor-3 in neurons after cerebral infarction. Ohba, N., Maeda, M., Nakagomi, S., Muraoka, M., Kiyama, H. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  5. Expression of the c-jun, jun-B, ets-2 and liver regeneration factor-1 (LRF-1) genes during promotion and progression of rat liver carcinogenesis in the resistant hepatocyte model. Liao, D.Z., Blanck, A., Gustafsson, J.A., Hällström, I.P. Cancer Lett. (1996) [Pubmed]
  6. Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. Hsu, J.C., Laz, T., Mohn, K.L., Taub, R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  7. Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration. Hsu, J.C., Bravo, R., Taub, R. Mol. Cell. Biol. (1992) [Pubmed]
  8. Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons. Lindwall, C., Dahlin, L., Lundborg, G., Kanje, M. Mol. Cell. Neurosci. (2004) [Pubmed]
  9. Activating transcription factor 3 mRNA is upregulated in primary cultures of trigeminal ganglion neurons. Dussor, G.O., Price, T.J., Flores, C.M. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  10. Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor. Weir, E., Chen, Q., DeFrances, M.C., Bell, A., Taub, R., Zarnegar, R. Hepatology (1994) [Pubmed]
  11. Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferation. Perez, S., Vial, E., van Dam, H., Castellazzi, M. Oncogene (2001) [Pubmed]
  12. Expression of activating transcription factor 3 and growth-associated protein 43 in the rat geniculate ganglion neurons after chorda tympani injury. Tsuzuki, K., Noguchi, K., Mohri, D., Yasuno, H., Umemoto, M., Shimobayashi, C., Fukazawa, K., Sakagami, M. Acta Otolaryngol. (2002) [Pubmed]
  13. Adenylyl cyclase type VI gene transfer reduces phospholamban expression in cardiac myocytes via activating transcription factor 3. Gao, M.H., Tang, T., Guo, T., Sun, S.Q., Feramisco, J.R., Hammond, H.K. J. Biol. Chem. (2004) [Pubmed]
  14. Exposure of the nucleus pulposus to the outside of the anulus fibrosus induces nerve injury and regeneration of the afferent fibers innervating the lumbar intervertebral discs in rats. Inoue, G., Ohtori, S., Aoki, Y., Ozawa, T., Doya, H., Saito, T., Ito, T., Akazawa, T., Moriya, H., Takahashi, K. Spine (2006) [Pubmed]
  15. Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury. Tsujino, H., Kondo, E., Fukuoka, T., Dai, Y., Tokunaga, A., Miki, K., Yonenobu, K., Ochi, T., Noguchi, K. Mol. Cell. Neurosci. (2000) [Pubmed]
  16. Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. Obata, K., Yamanaka, H., Kobayashi, K., Dai, Y., Mizushima, T., Katsura, H., Fukuoka, T., Tokunaga, A., Noguchi, K. J. Neurosci. (2004) [Pubmed]
  17. Distinct transcriptional changes in donor kidneys upon brain death induction in rats: insights in the processes of brain death. Schuurs, T.A., Gerbens, F., van der Hoeven, J.A., Ottens, P.J., Kooi, K.A., Leuvenink, H.G., Hofstra, R.M., Ploeg, R.J. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2004) [Pubmed]
  18. Spinal cord compression and dorsal root injury cause up-regulation of activating transcription factor-3 in large-diameter dorsal root ganglion neurons. Huang, W.L., Robson, D., Liu, M.C., King, V.R., Averill, S., Shortland, P.J., Priestley, J.V. Eur. J. Neurosci. (2006) [Pubmed]
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