ATF3

ATF3
Identifiers
Aliases	ATF3
External IDs	MGI: 109384 HomoloGene: 1265 GeneCards: ATF3
Gene ontology Molecular function • transcription regulatory region sequence-specific DNA binding • protein homodimerization activity • protein binding • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • protein heterodimerization activity • identical protein binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • DNA binding • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding • sequence-specific DNA binding • transcription regulatory region DNA binding • transcription corepressor activity • transcription factor activity, sequence-specific DNA binding Cellular component • nucleolus • nucleoplasm • CHOP-ATF3 complex • nucleus Biological process • regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • positive regulation of cell proliferation • skeletal muscle cell differentiation • regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance • gluconeogenesis • cellular response to amino acid starvation • negative regulation of transcription, DNA-templated • regulation of transcription, DNA-templated • positive regulation of TRAIL-activated apoptotic signaling pathway • transcription, DNA-templated • positive regulation of gene expression • PERK-mediated unfolded protein response • positive regulation of transcription from RNA polymerase II promoter • negative regulation of ERK1 and ERK2 cascade • negative regulation of transcription from RNA polymerase II promoter • endoplasmic reticulum unfolded protein response • transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	467	11910
Ensembl	ENSG00000162772	ENSMUSG00000026628
UniProt	P18847	Q60765
RefSeq (mRNA)	NM_001030287 NM_001040619 NM_001206484 NM_001206485 NM_001206486 NM_001206488 NM_001674 NM_004024	NM_007498
RefSeq (protein)	NP_001025458.1 NP_001035709.1 NP_001193413.2 NP_001193415.1 NP_001193417.2 NP_001665.1	NP_031524.2
Location (UCSC)	Chr 1: 212.57 – 212.62 Mb	Chr 1: 191.17 – 191.22 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

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

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.^[4]

Clinical significance

ATF-3 is induced upon physiological stress in various tissues.^[5] It is also a marker of regeneration following injury of dorsal root ganglion neurons in Pain Research.^[6]

See also

• Activating transcription factor

Interactions

ATF3 has been shown to interact with:

• C-jun,^[7][8][9]
• DDIT3^[8]
• JunD,^[10]
• P53,^[11][12] and
• SMAD3.^[13]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Chen BP, Liang G, Whelan J, Hai T (June 1994). "ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms". J Biol Chem. 269 (22): 15819–26. PMID 7515060.
4. "Entrez Gene: ATF3 activating transcription factor 3".
5. Chen BP, Wolfgang CD, Hai T (Mar 1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
6. Lindå H, Sköld MK, Ochsmann T (2011). "Activating transcription factor 3, a useful marker for regenerative response after nerve root injury". Front Neurol. 2: 30. doi:10.3389/fneur.2011.00030. PMC 3099310. PMID 21629765.
7. Pearson AG, Gray CW, Pearson JF, Greenwood JM, During MJ, Dragunow M (December 2003). "ATF3 enhances c-Jun-mediated neurite sprouting". Brain Res. Mol. Brain Res. 120 (1): 38–45. doi:10.1016/j.molbrainres.2003.09.014. PMID 14667575.
8. Chen BP, Wolfgang CD, Hai T (March 1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Mol. Cell. Biol. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
9. Hai T, Curran T (May 1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
10. Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Mol. Endocrinol. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
11. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
12. Yan C, Wang H, Boyd DD (March 2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". J. Biol. Chem. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID 11792711.
13. Kang Y, Chen CR, Massagué J (April 2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Mol. Cell. 11 (4): 915–26. doi:10.1016/s1097-2765(03)00109-6. PMID 12718878.

Further reading

• Hai TW, Liu F, Coukos WJ, Green MR (1990). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.". Genes Dev. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID 2516827.
• Kaszubska W, Hooft van Huijsduijnen R, Ghersa P, DeRaemy-Schenk AM, Chen BP, Hai T, DeLamarter JF, Whelan J (1993). "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.". Mol. Cell. Biol. 13 (11): 7180–90. PMC 364779. PMID 7692236.
• Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression.". Mol. Endocrinol. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
• Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T (1996). "ATF3 gene. Genomic organization, promoter, and regulation.". J. Biol. Chem. 271 (3): 1695–701. doi:10.1074/jbc.271.3.1695. PMID 8576171.
• Chen BP, Wolfgang CD, Hai T (1996). "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10.". Mol. Cell. Biol. 16 (3): 1157–68. doi:10.1128/MCB.16.3.1157. PMC 231098. PMID 8622660.
• Hagmeyer BM, Duyndam MC, Angel P, de Groot RP, Verlaan M, Elfferich P, van der Eb A, Zantema A (1996). "Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3.". Oncogene. 12 (5): 1025–32. PMID 8649793.
• Allan AL, Albanese C, Pestell RG, LaMarre J (2001). "Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes.". J. Biol. Chem. 276 (29): 27272–80. doi:10.1074/jbc.M103196200. PMID 11375399.
• Zhang C, Kawauchi J, Adachi MT, Hashimoto Y, Oshiro S, Aso T, Kitajima S (2002). "Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine.". Biochem. Biophys. Res. Commun. 289 (3): 718–24. doi:10.1006/bbrc.2001.6044. PMID 11726207.
• Yan C, Wang H, Boyd DD (2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter.". J. Biol. Chem. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID 11792711.
• Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles.". J. Biomed. Sci. 9 (1): 82–96. doi:10.1007/BF02256581. PMID 11810028.
• Hashimoto Y, Zhang C, Kawauchi J, Imoto I, Adachi MT, Inazawa J, Amagasa T, Hai T, Kitajima S (2002). "An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli.". Nucleic Acids Res. 30 (11): 2398–406. doi:10.1093/nar/30.11.2398. PMC 117192. PMID 12034827.
• Kawauchi J, Zhang C, Nobori K, Hashimoto Y, Adachi MT, Noda A, Sunamori M, Kitajima S (2002). "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.". J. Biol. Chem. 277 (41): 39025–34. doi:10.1074/jbc.M202974200. PMID 12161427.
• Zhang C, Gao C, Kawauchi J, Hashimoto Y, Tsuchida N, Kitajima S (2002). "Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53.". Biochem. Biophys. Res. Commun. 297 (5): 1302–10. doi:10.1016/S0006-291X(02)02382-3. PMID 12372430.
• Fan F, Jin S, Amundson SA, Tong T, Fan W, Zhao H, Zhu X, Mazzacurati L, Li X, Petrik KL, Fornace AJ, Rajasekaran B, Zhan Q (2002). "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. doi:10.1038/sj.onc.1205896. PMID 12386811.
• Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M (2003). "ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3.". J. Mol. Cell. Cardiol. 34 (10): 1387–97. doi:10.1006/jmcc.2002.2091. PMID 12392999.
• Kang Y, Chen CR, Massagué J (2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells.". Mol. Cell. 11 (4): 915–26. doi:10.1016/S1097-2765(03)00109-6. PMID 12718878.
• Newman JR, Keating AE (2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays.". Science. 300 (5628): 2097–101. doi:10.1126/science.1084648. PMID 12805554.
• Kool J, Hamdi M, Cornelissen-Steijger P, van der Eb AJ, Terleth C, van Dam H (2003). "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. doi:10.1038/sj.onc.1206611. PMID 12833146.

External links

• 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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