View source for DNA damage-inducible transcript 3

{{Infobox_gene}}
'''DNA damage-inducible transcript 3''', also known as '''C/EBP homologous protein (CHOP)''', is a pro-[[apoptosis|apoptotic]] [[transcription factor]] that is encoded by the ''DDIT3'' [[gene]].<ref name="pmid1990262">{{cite journal | vauthors = Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, ((Alamo I Jr)), Barrett SF, Hickson ID, ((Fornace AJ Jr)) | title = Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C | journal = Mol Cell Biol | volume = 11 | issue = 2 | pages = 1009–16 |date=March 1991 | pmid = 1990262 | pmc = 359769 | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DDIT3 DNA-damage-inducible transcript 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1649| accessdate = }}</ref>

== Interactions ==

DNA damage-inducible transcript 3 has been shown to [[Protein-protein interaction|interact]] with [proteins]:
{{div col|colwidth=20em}}
* [[ATF3]],<ref name = pmid8622660>{{cite journal | date = March 1996 | vauthors = Chen BP, Wolfgang CD, Hai T | title = Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10 | journal = Mol. Cell. Biol. | volume = 16 | issue = 3 | pages = 1157–68 | pmid = 8622660 | pmc = 231098 | doi = 10.1128/MCB.16.3.1157}}</ref> 
* [[C-Fos]],<ref name = pmid10523647/>
* [[C-jun]]<ref name = pmid10523647/> and 
* [[CEBPB]],<ref name = pmid12706815>{{cite journal | date = April 2003 | vauthors = Hattori T, Ohoka N, Hayashi H, Onozaki K | title = C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform | journal = FEBS Lett. | volume = 541 | issue = 1-3 | pages = 33–9 | pmid = 12706815 | doi = 10.1016/s0014-5793(03)00283-7}}</ref><ref name = pmid8662954>{{cite journal | date = June 1996 | vauthors = Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ | title = Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress | journal = J. Biol. Chem. | volume = 271 | issue = 24 | pages = 14285–9 | pmid = 8662954 | doi = 10.1074/jbc.271.24.14285}}</ref> 
* [[Casein kinase 2, alpha 1|CSNK2A1]],<ref name = pmid12876286>{{cite journal | date = October 2003 | vauthors = Ubeda M, Habener JF | title = CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation | journal = J. Biol. Chem. | volume = 278 | issue = 42 | pages = 40514–20 | pmid = 12876286 | doi = 10.1074/jbc.M306404200}}</ref> 
* [[JunD]],<ref name = pmid10523647>{{cite journal | date = November 1999 | vauthors = Ubeda M, Vallejo M, Habener JF | title = CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 11 | pages = 7589–99 | pmid = 10523647 | pmc = 84780 | doi = }}</ref>  and
* [[RPS3A]].<ref name = pmid10713066>{{cite journal | date = March 2000 | vauthors = Cui K, Coutts M, Stahl J, Sytkowski AJ | title = Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis | journal = J. Biol. Chem. | volume = 275 | issue = 11 | pages = 7591–6 | pmid = 10713066 | doi = 10.1074/jbc.275.11.7591}}</ref> 
{{Div col end}}

==Clinical significance==
During [[endoplasmic reticulum]] stress (such as [[Endoplasmic reticulum stress in beta cells|occurs in beta cells of the pancreas]] or in [[macrophage]]s causing [[atherosclerosis]]), CHOP can induce activation of [[ER oxidoreductin|Ero1]], causing calcium release from the endoplasmic reticulum into the [[cytoplasm]], resulting in [[apoptosis]].<ref name="pmid19752026">{{cite journal | vauthors=Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I | title=Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis | journal= [[Journal of Cell Biology]] | volume=186 | issue=6 | pages=783-792 | year=2009 | url=http://jcb.rupress.org/content/186/6/783.long | DOI=10.1083/jcb.200904060 | PMC=2753154 | PMID = 19752026 }}</ref>  CHOP also induces apoptosis during endoplasmic reticulum stress by activating [[PPP1R15A|growth arrest and DNA damage-inducible protein GADD34]].<ref name="pmid15601821">{{cite journal | vauthors=Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP, Ron D | title=CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum | journal= [[Genes & Development]] | volume=18 | issue=24 | pages=3066-3077 | year=2004 | url=http://genesdev.cshlp.org/content/18/24/3066.long | DOI=10.1101/gad.1250704 | PMC=535917 | PMID = 15601821 }}</ref> 

Mutations or fusions of CHOP (e.g. with [[FUS (gene)|FUS]] to form '''[[FUS-CHOP]]''') can cause [[Myxoid liposarcoma]].<ref name=Panag1996>{{cite journal  | author=Panagopoulos I |title=Fusion of the EWS and CHOP genes in myxoid liposarcoma |journal=Oncogene |volume=12 |issue= 3 |pages= 489–94 |year= 1996 |pmid= 8637704 |doi=  |name-list-format=vanc| author2=Höglund M  | author3=Mertens F  | display-authors=3  | last4=Mandahl  | first4=N  | last5=Mitelman  | first5=F  | last6=Aman  | first6=P  }}</ref>

== References ==
{{reflist}}

==Further reading==
{{refbegin|35em}}
*{{cite journal  | vauthors=Ramji DP, Foka P |title=CCAAT/enhancer-binding proteins: structure, function and regulation |journal=Biochem. J. |volume=365 |issue= Pt 3 |pages= 561–75 |year= 2002 |pmid= 12006103 |doi= 10.1042/BJ20020508  | pmc=1222736 }}
*{{cite journal  | vauthors=Oyadomari S, Mori M |title=Roles of CHOP/GADD153 in endoplasmic reticulum stress |journal=Cell Death Differ. |volume=11 |issue= 4 |pages= 381–9 |year= 2004 |pmid= 14685163 |doi= 10.1038/sj.cdd.4401373 }}
*{{cite journal  | author=Aman P |title=Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11) |journal=Genes Chromosomes Cancer |volume=5 |issue= 4 |pages= 278–85 |year= 1993 |pmid= 1283316 |doi=10.1002/gcc.2870050403  |name-list-format=vanc| author2=Ron D  | author3=Mandahl N  | display-authors=3  | last4=Fioretos  | first4=Thoas  | last5=Heim  | first5=Sverre  | last6=Arheden  | first6=Kristina  | last7=Willén  | first7=Helena  | last8=Rydholm  | first8=Anders  | last9=Mitelman  | first9=Felix  }}
*{{cite journal  | author=Park JS |title=Isolation, characterization and chromosomal localization of the human GADD153 gene |journal=Gene |volume=116 |issue= 2 |pages= 259–67 |year= 1992 |pmid= 1339368 |doi=10.1016/0378-1119(92)90523-R  |name-list-format=vanc| author2=Luethy JD  | author3=Wang MG  | display-authors=3  | last4=Fargnoli  | first4=Joseph  | last5=Fornace  | first5=Albert J  | last6=Wesley Mcbride  | first6=O  | last7=Holbrook  | first7=Nikki J  }}
*{{cite journal  | vauthors=Ron D, Habener JF |title=CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription |journal=Genes Dev. |volume=6 |issue= 3 |pages= 439–53 |year= 1992 |pmid= 1547942 |doi=10.1101/gad.6.3.439  }}
*{{cite journal  | author=Eneroth M |title=Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2 |journal=Cancer Genet. Cytogenet. |volume=48 |issue= 1 |pages= 101–7 |year= 1990 |pmid= 2372777 |doi=10.1016/0165-4608(90)90222-V  |name-list-format=vanc| author2=Mandahl N  | author3=Heim S  | display-authors=3  | last4=Willen  | first4=H  | last5=Rydholm  | first5=A  | last6=Alberts  | first6=K  | last7=Mitelman  | first7=F  }}
*{{cite journal  | vauthors=Rabbitts TH, Forster A, Larson R, Nathan P |title=Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma |journal=Nat. Genet. |volume=4 |issue= 2 |pages= 175–80 |year= 1993 |pmid= 7503811 |doi= 10.1038/ng0693-175 }}
*{{cite journal  | vauthors=Crozat A, Aman P, Mandahl N, Ron D |title=Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma |journal=Nature |volume=363 |issue= 6430 |pages= 640–4 |year= 1993 |pmid= 8510758 |doi= 10.1038/363640a0 }}
*{{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=Mol. Cell. Biol. |volume=16 |issue= 3 |pages= 1157–68 |year= 1996 |pmid= 8622660 |doi=  10.1128/MCB.16.3.1157| pmc=231098  }}
*{{cite journal  | vauthors=Wang XZ, Ron D |title=Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase |journal=Science |volume=272 |issue= 5266 |pages= 1347–9 |year= 1996 |pmid= 8650547 |doi=10.1126/science.272.5266.1347  }}
*{{cite journal  | vauthors=Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ |title=Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress |journal=J. Biol. Chem. |volume=271 |issue= 24 |pages= 14285–9 |year= 1996 |pmid= 8662954 |doi=10.1074/jbc.271.24.14285  }}
*{{cite journal  | vauthors=Ubeda M, Vallejo M, Habener JF |title=CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins |journal=Mol. Cell. Biol. |volume=19 |issue= 11 |pages= 7589–99 |year= 1999 |pmid= 10523647 |doi=  | pmc=84780  }}
*{{cite journal  | vauthors=Cui K, Coutts M, Stahl J, Sytkowski AJ |title=Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis |journal=J. Biol. Chem. |volume=275 |issue= 11 |pages= 7591–6 |year= 2000 |pmid= 10713066 |doi=10.1074/jbc.275.11.7591  }}
*{{cite journal  | vauthors=Gotoh T, Oyadomari S, Mori K, Mori M |title=Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP |journal=J. Biol. Chem. |volume=277 |issue= 14 |pages= 12343–50 |year= 2002 |pmid= 11805088 |doi= 10.1074/jbc.M107988200 }}
*{{cite journal  | author=Satoh T |title=Activation of peroxisome proliferator-activated receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells |journal=Oncogene |volume=21 |issue= 14 |pages= 2171–80 |year= 2002 |pmid= 11948400 |doi= 10.1038/sj.onc.1205279  |name-list-format=vanc| author2=Toyoda M  | author3=Hoshino H  | display-authors=3  | last4=Monden  | first4=Tsuyoshi  | last5=Yamada  | first5=Masanabu  | last6=Shimizu  | first6=Hiroyuki  | last7=Miyamoto  | first7=Kaoru  | last8=Mori  | first8=Matsumoto }}
*{{cite journal  | vauthors=Qiao D, Im E, Qi W, Martinez JD |title=Activator protein-1 and CCAAT/enhancer-binding protein mediated GADD153 expression is involved in deoxycholic acid-induced apoptosis |journal=Biochim. Biophys. Acta |volume=1583 |issue= 1 |pages= 108–16 |year= 2002 |pmid= 12069855 |doi=  10.1016/s1388-1981(02)00190-7}}
*{{cite journal  | vauthors=Talukder AH, Wang RA, Kumar R |title=Expression and transactivating functions of the bZIP transcription factor GADD153 in mammary epithelial cells |journal=Oncogene |volume=21 |issue= 27 |pages= 4289–300 |year= 2002 |pmid= 12082616 |doi= 10.1038/sj.onc.1205529 }}
{{refend}}

== External links ==
* {{MeshName|DDIT3+protein,+human}}

{{NLM content}}
{{Transcription factors|g1}}

[[Category:Transcription factors]]
[[Category:Oncogenes]]