View source for Biology:ATF3

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Cyclic AMP-dependent transcription factor ATF-3''' is a [[Biology:Protein|protein]] that, in humans, is encoded by the ''ATF3'' [[Biology:Gene|gene]].<ref name="pmid7515060">{{cite journal | vauthors = Chen BP, Liang G, Whelan J, Hai T | title = ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms | journal = The Journal of Biological Chemistry | volume = 269 | issue = 22 | pages = 15819–26 | date = June 1994 | doi = 10.1016/S0021-9258(17)40754-X | pmid = 7515060 | doi-access = free }}</ref>

== Function ==

Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding ([[Biology:CREB|CREB]]) protein family of [[Biology:Transcription factor|transcription factor]]s. 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 [[Biology:Leucine zipper|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.<ref name="entrez">{{cite web | title = Entrez Gene: ATF3 activating transcription factor 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=467}}</ref>

== Clinical significance ==

''ATF-3'' is induced upon physiological stress in various tissues.<ref>{{cite journal | vauthors = Chen BP, Wolfgang CD, Hai T | title = Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10 | journal = Molecular and Cellular Biology | volume = 16 | issue = 3 | pages = 1157–68 | date = March 1996 | pmid = 8622660 | pmc = 231098 | doi = 10.1128/MCB.16.3.1157 }}</ref> It is also a marker of regeneration following injury of dorsal root ganglion neurons, as injured regenerating neurons activate this transcription factor. <ref name="pmid21629765">{{cite journal | vauthors = Lindå H, Sköld MK, Ochsmann T | title = Activating transcription factor 3, a useful marker for regenerative response after nerve root injury | journal = Frontiers in Neurology | volume = 2 | pages = 30 | year = 2011 | pmid = 21629765 | pmc = 3099310 | doi = 10.3389/fneur.2011.00030 | doi-access = free }}</ref> 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. <ref>{{cite journal | vauthors = Mahar M, Cavalli V | title = Intrinsic mechanisms of neuronal axon regeneration | language = En | journal = Nature Reviews. Neuroscience | volume = 19 | issue = 6 | pages = 323–337 | date = June 2018 | pmid = 29666508 | pmc = 5987780 | doi = 10.1038/s41583-018-0001-8 }}</ref>

== See also ==
* [[Biology:Activating transcription factor|Activating transcription factor]]

== Interactions ==
ATF3 has been shown to interact with:
* C-jun,<ref name = pmid14667575>{{cite journal | vauthors = Pearson AG, Gray CW, Pearson JF, Greenwood JM, During MJ, Dragunow M | title = ATF3 enhances c-Jun-mediated neurite sprouting | journal = Brain Research. Molecular Brain Research | volume = 120 | issue = 1 | pages = 38–45 | date = December 2003 | pmid = 14667575 | doi = 10.1016/j.molbrainres.2003.09.014 }}</ref><ref name = pmid8622660>{{cite journal | vauthors = Chen BP, Wolfgang CD, Hai T | title = Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10 | journal = Molecular and Cellular Biology | volume = 16 | issue = 3 | pages = 1157–68 | date = March 1996 | pmid = 8622660 | pmc = 231098 | doi = 10.1128/MCB.16.3.1157 }}</ref><ref name = pmid1827203>{{cite journal | vauthors = Hai T, Curran T | title = Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 9 | pages = 3720–4 | date = May 1991 | pmid = 1827203 | pmc = 51524 | doi = 10.1073/pnas.88.9.3720 | bibcode = 1991PNAS...88.3720H | doi-access = free }}</ref> 
* [[Biology:DNA damage-inducible transcript 3|DDIT3]]<ref name = pmid8622660/> 
* [[Biology:JunD|JunD]],<ref name = pmid8152431>{{cite journal | vauthors = Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ | title = Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression | journal = Molecular Endocrinology | volume = 8 | issue = 1 | pages = 59–68 | date = January 1994 | pmid = 8152431 | doi = 10.1210/mend.8.1.8152431 | doi-access = free }}</ref> 
* [[Biology:P53|P53]],<ref name = pmid16169070>{{cite journal | vauthors = 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 | title = A human protein-protein interaction network: a resource for annotating the proteome | journal = Cell | volume = 122 | issue = 6 | pages = 957–68 | date = September 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 | hdl = 11858/00-001M-0000-0010-8592-0 | s2cid = 8235923 | hdl-access = free }}</ref><ref name = pmid11792711>{{cite journal | vauthors = Yan C, Wang H, Boyd DD | title = ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter | journal = The Journal of Biological Chemistry | volume = 277 | issue = 13 | pages = 10804–12 | date = March 2002 | pmid = 11792711 | doi = 10.1074/jbc.M112069200 | doi-access = free }}</ref> and
* [[Biology:Mothers against decapentaplegic homolog 3|SMAD3]].<ref name = pmid12718878>{{cite journal | vauthors = Kang Y, Chen CR, Massagué J | title = A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells | journal = Molecular Cell | volume = 11 | issue = 4 | pages = 915–26 | date = April 2003 | pmid = 12718878 | doi = 10.1016/s1097-2765(03)00109-6 | doi-access = free }}</ref>
{{clear}}

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin|35em}}
* {{cite journal | vauthors = Hai TW, Liu F, Coukos WJ, Green MR | title = Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers | journal = Genes & Development | volume = 3 | issue = 12B | pages = 2083–90 | date = December 1989 | pmid = 2516827 | doi = 10.1101/gad.3.12b.2083 | doi-access = free }}
* {{cite journal | vauthors = Kaszubska W, Hooft van Huijsduijnen R, Ghersa P, DeRaemy-Schenk AM, Chen BP, Hai T, DeLamarter JF, Whelan J | title = 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 | journal = Molecular and Cellular Biology | volume = 13 | issue = 11 | pages = 7180–90 | date = November 1993 | pmid = 7692236 | pmc = 364779 | doi =  10.1128/MCB.13.11.7180}}
* {{cite journal | vauthors = Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ | title = Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression | journal = Molecular Endocrinology | volume = 8 | issue = 1 | pages = 59–68 | date = January 1994 | pmid = 8152431 | doi = 10.1210/mend.8.1.8152431 | doi-access = free }}
* {{cite journal | vauthors = Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T | title = ATF3 gene. Genomic organization, promoter, and regulation | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1695–701 | date = January 1996 | pmid = 8576171 | doi = 10.1074/jbc.271.3.1695 | doi-access = free }}
* {{cite journal | vauthors = Chen BP, Wolfgang CD, Hai T | title = Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10 | journal = Molecular and Cellular Biology | volume = 16 | issue = 3 | pages = 1157–68 | date = March 1996 | pmid = 8622660 | pmc = 231098 | doi = 10.1128/MCB.16.3.1157 }}
* {{cite journal | vauthors = Hagmeyer BM, Duyndam MC, Angel P, de Groot RP, Verlaan M, Elfferich P, van der Eb A, Zantema A | title = Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3 | journal = Oncogene | volume = 12 | issue = 5 | pages = 1025–32 | date = March 1996 | pmid = 8649793 }}
* {{cite journal | vauthors = Allan AL, Albanese C, Pestell RG, LaMarre J | title = Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes | journal = The Journal of Biological Chemistry | volume = 276 | issue = 29 | pages = 27272–80 | date = July 2001 | pmid = 11375399 | doi = 10.1074/jbc.M103196200 | doi-access = free }}
* {{cite journal | vauthors = Zhang C, Kawauchi J, Adachi MT, Hashimoto Y, Oshiro S, Aso T, Kitajima S | title = Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine | journal = Biochemical and Biophysical Research Communications | volume = 289 | issue = 3 | pages = 718–24 | date = December 2001 | pmid = 11726207 | doi = 10.1006/bbrc.2001.6044 }}
* {{cite journal | vauthors = Yan C, Wang H, Boyd DD | title = ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter | journal = The Journal of Biological Chemistry | volume = 277 | issue = 13 | pages = 10804–12 | date = March 2002 | pmid = 11792711 | doi = 10.1074/jbc.M112069200 | doi-access = free }}
* {{cite journal | vauthors = Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S | title = Effects of HIV-1 Nef on cellular gene expression profiles | journal = Journal of Biomedical Science | volume = 9 | issue = 1 | pages = 82–96 | year = 2002 | pmid = 11810028 | doi = 10.1007/BF02256581 }}
* {{cite journal | vauthors = Hashimoto Y, Zhang C, Kawauchi J, Imoto I, Adachi MT, Inazawa J, Amagasa T, Hai T, Kitajima S | title = An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli | journal = Nucleic Acids Research | volume = 30 | issue = 11 | pages = 2398–406 | date = June 2002 | pmid = 12034827 | pmc = 117192 | doi = 10.1093/nar/30.11.2398 }}
* {{cite journal | vauthors = Kawauchi J, Zhang C, Nobori K, Hashimoto Y, Adachi MT, Noda A, Sunamori M, Kitajima S | title = 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 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 41 | pages = 39025–34 | date = October 2002 | pmid = 12161427 | doi = 10.1074/jbc.M202974200 | doi-access = free }}
* {{cite journal | vauthors = Zhang C, Gao C, Kawauchi J, Hashimoto Y, Tsuchida N, Kitajima S | title = Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53 | journal = Biochemical and Biophysical Research Communications | volume = 297 | issue = 5 | pages = 1302–10 | date = October 2002 | pmid = 12372430 | doi = 10.1016/S0006-291X(02)02382-3 }}
* {{cite journal | vauthors = 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 | title = ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth | journal = Oncogene | volume = 21 | issue = 49 | pages = 7488–96 | date = October 2002 | pmid = 12386811 | doi = 10.1038/sj.onc.1205896 | doi-access = free }}
* {{cite journal | vauthors = Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M | title = ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3 | journal = Journal of Molecular and Cellular Cardiology | volume = 34 | issue = 10 | pages = 1387–97 | date = October 2002 | pmid = 12392999 | doi = 10.1006/jmcc.2002.2091 }}
* {{cite journal | vauthors = Kang Y, Chen CR, Massagué J | title = A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells | journal = Molecular Cell | volume = 11 | issue = 4 | pages = 915–26 | date = April 2003 | pmid = 12718878 | doi = 10.1016/S1097-2765(03)00109-6 | doi-access = free }}
* {{cite journal | vauthors = Newman JR, Keating AE | title = Comprehensive identification of human bZIP interactions with coiled-coil arrays | journal = Science | volume = 300 | issue = 5628 | pages = 2097–101 | date = June 2003 | pmid = 12805554 | doi = 10.1126/science.1084648 | bibcode = 2003Sci...300.2097N | s2cid = 36715183 | doi-access = free }}
* {{cite journal | vauthors = Kool J, Hamdi M, Cornelissen-Steijger P, van der Eb AJ, Terleth C, van Dam H | title = Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2 | journal = Oncogene | volume = 22 | issue = 27 | pages = 4235–42 | date = July 2003 | pmid = 12833146 | doi = 10.1038/sj.onc.1206611 | doi-access = free }}
{{refend}}

== External links ==
* {{UCSC gene info|ATF3}}
* {{MeshName|ATF3+protein,+human}}
* {{FactorBook|ATF3}}
{{NLM content}}

{{Regulome
| activates = 
| inhibits = [[Biology:MMP2|MMP2]], [[Biology:Adiponectin|adiponectin]]<ref name="pmid17827403 group = note">{{cite journal | vauthors = Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim MS, Kim SW, Park IS, Youn JH, Lee KU | title = Essential role of mitochondrial function in adiponectin synthesis in adipocytes | journal = Diabetes | volume = 56 | issue = 12 | pages = 2973–81 | date = December 2007 | pmid = 17827403 | doi = 10.2337/db07-0510 | doi-access = free }}</ref>
| activated_by = not
| inhibited_by = 
}}
{{Transcription factors|g1}}

[[Category:Transcription factors]]

{{Sourceattribution|ATF3}}