Biology:ATF3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.

Function

Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. Multiple transcript variants encoding two different isoforms have been found for this gene. The longer isoform represses rather than activates transcription from promoters with ATF binding elements. The shorter isoform (deltaZip2) lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription, it is presumed, by sequestering inhibitory co-factors away from the promoter. It is possible that alternative splicing of the ATF3 gene may be physiologically important in the regulation of target genes.

Clinical significance

ATF-3 is induced upon physiological stress in various tissues. It is also a marker of regeneration following injury of dorsal root ganglion neurons, as injured regenerating neurons activate this transcription factor. Functional validation studies have shown that ATF3 can promote regeneration of peripheral neurons, but is not capable of promoting regeneration of central nervous system neurons.

See also

• Activating transcription factor

Interactions

ATF3 has been shown to interact with:

• C-jun,
• DDIT3
• JunD,
• P53, and
• SMAD3.

Further reading

• "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes & Development 3 (12B): 2083–90. December 1989. doi:10.1101/gad.3.12b.2083. PMID 2516827. 
• "Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines". Molecular and Cellular Biology 13 (11): 7180–90. November 1993. doi:10.1128/MCB.13.11.7180. PMID 7692236. 
• "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Molecular Endocrinology 8 (1): 59–68. January 1994. doi:10.1210/mend.8.1.8152431. PMID 8152431. 
• "ATF3 gene. Genomic organization, promoter, and regulation". The Journal of Biological Chemistry 271 (3): 1695–701. January 1996. doi:10.1074/jbc.271.3.1695. PMID 8576171. 
• "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology 16 (3): 1157–68. March 1996. doi:10.1128/MCB.16.3.1157. PMID 8622660. 
• "Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3". Oncogene 12 (5): 1025–32. March 1996. PMID 8649793. 
• "Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes". The Journal of Biological Chemistry 276 (29): 27272–80. July 2001. doi:10.1074/jbc.M103196200. PMID 11375399. 
• "Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine". Biochemical and Biophysical Research Communications 289 (3): 718–24. December 2001. doi:10.1006/bbrc.2001.6044. PMID 11726207. 
• "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". The Journal of Biological Chemistry 277 (13): 10804–12. March 2002. doi:10.1074/jbc.M112069200. PMID 11792711. 
• "Effects of HIV-1 Nef on cellular gene expression profiles". Journal of Biomedical Science 9 (1): 82–96. 2002. doi:10.1007/BF02256581. PMID 11810028. 
• "An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli". Nucleic Acids Research 30 (11): 2398–406. June 2002. doi:10.1093/nar/30.11.2398. PMID 12034827. 
• "Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription". The Journal of Biological Chemistry 277 (41): 39025–34. October 2002. doi:10.1074/jbc.M202974200. PMID 12161427. 
• "Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53". Biochemical and Biophysical Research Communications 297 (5): 1302–10. October 2002. doi:10.1016/S0006-291X(02)02382-3. PMID 12372430. 
• "ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth". Oncogene 21 (49): 7488–96. October 2002. doi:10.1038/sj.onc.1205896. PMID 12386811. 
• "ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3". Journal of Molecular and Cellular Cardiology 34 (10): 1387–97. October 2002. doi:10.1006/jmcc.2002.2091. PMID 12392999. 
• "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Molecular Cell 11 (4): 915–26. April 2003. doi:10.1016/S1097-2765(03)00109-6. PMID 12718878. 
• "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science 300 (5628): 2097–101. June 2003. doi:10.1126/science.1084648. PMID 12805554. Bibcode: 2003Sci...300.2097N. 
• "Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2". Oncogene 22 (27): 4235–42. July 2003. doi:10.1038/sj.onc.1206611. PMID 12833146. 

External links

• Human ATF3 genome location and ATF3 gene details page in the UCSC Genome Browser.
• ATF3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook ATF3

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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