DNA damage-inducible transcript 3

DNA-damage-inducible transcript 3
Identifiers
Symbols	DDIT3 ; CEBPZ; CHOP; CHOP-10; CHOP10; GADD153
External IDs	OMIM: 126337 MGI: 109247 HomoloGene: 3012 GeneCards: DDIT3 Gene
Gene ontology Molecular function • transcription regulatory region sequence-specific DNA binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • transcription factor activity, sequence-specific DNA binding • transcription corepressor activity • protein binding • transcription factor binding • cAMP response element binding protein binding • protein homodimerization activity • leucine zipper domain binding • transcription regulatory region DNA binding • protein heterodimerization activity Cellular component • nucleus • nucleoplasm • late endosome • cytosol • protein-DNA complex • AP1 complex • CHOP-C/EBP complex • CHOP-ATF4 complex • CHOP-ATF3 complex Biological process • negative regulation of transcription from RNA polymerase II promoter • blood vessel maturation • regulation of transcription, DNA-templated • cellular response to DNA damage stimulus • ER overload response • response to unfolded protein • cell cycle arrest • Wnt signaling pathway • endoplasmic reticulum unfolded protein response • positive regulation of interleukin-8 production • negative regulation of CREB transcription factor activity • response to endoplasmic reticulum stress • PERK-mediated unfolded protein response • ATF6-mediated unfolded protein response • response to starvation • mRNA transcription from RNA polymerase II promoter • proteasome-mediated ubiquitin-dependent protein catabolic process • negative regulation of sequence-specific DNA binding transcription factor activity • positive regulation of neuron apoptotic process • regulation of DNA-templated transcription in response to stress • cellular protein metabolic process • regulation of transcription involved in anterior/posterior axis specification • cell redox homeostasis • negative regulation of fat cell differentiation • negative regulation of myoblast differentiation • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • release of sequestered calcium ion into cytosol • negative regulation of protein kinase B signaling • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • negative regulation of canonical Wnt signaling pathway • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • negative regulation of determination of dorsal identity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1649	13198
Ensembl	ENSG00000175197	ENSMUSG00000025408
UniProt	P35638	P35639
RefSeq (mRNA)	NM_001195053	NM_001290183
RefSeq (protein)	NP_001181982	NP_001277112
Location (UCSC)	Chr 12: 57.52 – 57.52 Mb	Chr 10: 127.29 – 127.3 Mb
PubMed search

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a transcription factor that is encoded by the DDIT3 gene.^[1][2]

Interactions

DNA damage-inducible transcript 3 has been shown to interact with [proteins]:

• ATF3,^[3]
• C-Fos,^[4]
• C-jun^[4] and
• CEBPB,^[5][6]
• CSNK2A1,^[7]
• JunD,^[4] and
• RPS3A.^[8]

Clinical significance

Mutations or fusions of CHOP (eg with FUS to form FUS-CHOP) can cause Myxoid liposarcoma.^[9]

References

1. Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, Alamo I Jr, Barrett SF, Hickson ID, Fornace AJ Jr (March 1991). "Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C". Mol Cell Biol 11 (2): 1009–16. PMC 359769. PMID 1990262.
2. "Entrez Gene: DDIT3 DNA-damage-inducible transcript 3".
3. 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. PMC 231098. PMID 8622660.
4. Ubeda M, Vallejo M, Habener JF (November 1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. 19 (11): 7589–99. PMC 84780. PMID 10523647.
5. Hattori T, Ohoka N, Hayashi H, Onozaki K (April 2003). "C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform". FEBS Lett. 541 (1-3): 33–9. doi:10.1016/s0014-5793(03)00283-7. PMID 12706815.
6. Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ (June 1996). "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". J. Biol. Chem. 271 (24): 14285–9. doi:10.1074/jbc.271.24.14285. PMID 8662954.
7. Ubeda M, Habener JF (October 2003). "CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation". J. Biol. Chem. 278 (42): 40514–20. doi:10.1074/jbc.M306404200. PMID 12876286.
8. Cui K, Coutts M, Stahl J, Sytkowski AJ (March 2000). "Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis". J. Biol. Chem. 275 (11): 7591–6. doi:10.1074/jbc.275.11.7591. PMID 10713066.
9. Panagopoulos I, Höglund M, Mertens F, et al. (1996). "Fusion of the EWS and CHOP genes in myxoid liposarcoma". Oncogene 12 (3): 489–94. PMID 8637704.

Further reading

• Ramji DP, Foka P (2002). "CCAAT/enhancer-binding proteins: structure, function and regulation". Biochem. J. 365 (Pt 3): 561–75. doi:10.1042/BJ20020508. PMC 1222736. PMID 12006103.
• Oyadomari S, Mori M (2004). "Roles of CHOP/GADD153 in endoplasmic reticulum stress". Cell Death Differ. 11 (4): 381–9. doi:10.1038/sj.cdd.4401373. PMID 14685163.
• Aman P, Ron D, Mandahl N, et al. (1993). "Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11)". Genes Chromosomes Cancer 5 (4): 278–85. doi:10.1002/gcc.2870050403. PMID 1283316.
• Park JS, Luethy JD, Wang MG, et al. (1992). "Isolation, characterization and chromosomal localization of the human GADD153 gene". Gene 116 (2): 259–67. doi:10.1016/0378-1119(92)90523-R. PMID 1339368.
• Ron D, Habener JF (1992). "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". Genes Dev. 6 (3): 439–53. doi:10.1101/gad.6.3.439. PMID 1547942.
• Eneroth M, Mandahl N, Heim S, et al. (1990). "Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2". Cancer Genet. Cytogenet. 48 (1): 101–7. doi:10.1016/0165-4608(90)90222-V. PMID 2372777.
• Rabbitts TH, Forster A, Larson R, Nathan P (1993). "Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma". Nat. Genet. 4 (2): 175–80. doi:10.1038/ng0693-175. PMID 7503811.
• Crozat A, Aman P, Mandahl N, Ron D (1993). "Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma". Nature 363 (6430): 640–4. doi:10.1038/363640a0. PMID 8510758.
• 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. PMC 231098. PMID 8622660.
• Wang XZ, Ron D (1996). "Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase". Science 272 (5266): 1347–9. doi:10.1126/science.272.5266.1347. PMID 8650547.
• Fawcett TW, Eastman HB, Martindale JL, Holbrook NJ (1996). "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". J. Biol. Chem. 271 (24): 14285–9. doi:10.1074/jbc.271.24.14285. PMID 8662954.
• Ubeda M, Vallejo M, Habener JF (1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. 19 (11): 7589–99. PMC 84780. PMID 10523647.
• Cui K, Coutts M, Stahl J, Sytkowski AJ (2000). "Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis". J. Biol. Chem. 275 (11): 7591–6. doi:10.1074/jbc.275.11.7591. PMID 10713066.
• Gotoh T, Oyadomari S, Mori K, Mori M (2002). "Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP". J. Biol. Chem. 277 (14): 12343–50. doi:10.1074/jbc.M107988200. PMID 11805088.
• Satoh T, Toyoda M, Hoshino H, et al. (2002). "Activation of peroxisome proliferator-activated receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells". Oncogene 21 (14): 2171–80. doi:10.1038/sj.onc.1205279. PMID 11948400.
• Qiao D, Im E, Qi W, Martinez JD (2002). "Activator protein-1 and CCAAT/enhancer-binding protein mediated GADD153 expression is involved in deoxycholic acid-induced apoptosis". Biochim. Biophys. Acta 1583 (1): 108–16. doi:10.1016/s1388-1981(02)00190-7. PMID 12069855.
• Talukder AH, Wang RA, Kumar R (2002). "Expression and transactivating functions of the bZIP transcription factor GADD153 in mammary epithelial cells". Oncogene 21 (27): 4289–300. doi:10.1038/sj.onc.1205529. PMID 12082616.

External links

• DDIT3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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