DNA damage-inducible transcript 3

DDIT3
Identifiers
AliasesDDIT3, CEBPZ, CHOP, CHOP-10, CHOP10, GADD153, DNA damage-inducible transcript 3, DNA damage inducible transcript 3, C/EBPzeta
External IDsMGI: 109247 HomoloGene: 3012 GeneCards: DDIT3
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q13.3Start57,516,588 bp[1]
End57,521,737 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1649

13198

Ensembl

ENSG00000175197

ENSMUSG00000025408

UniProt

P35638

P35639

RefSeq (mRNA)

NM_001290183
NM_007837

RefSeq (protein)

NP_001277112
NP_031863

Location (UCSC)Chr 12: 57.52 – 57.52 MbChr 10: 127.29 – 127.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene.[5][6]

Interactions

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

Clinical significance

During endoplasmic reticulum stress (such as occurs in beta cells of the pancreas or in macrophages causing atherosclerosis), CHOP can induce activation of Ero1, causing calcium release from the endoplasmic reticulum into the cytoplasm, resulting in apoptosis.[13] CHOP also induces apoptosis during endoplasmic reticulum stress by activating growth arrest and DNA damage-inducible protein GADD34.[14]

Mutations or fusions of CHOP (e.g. with FUS to form FUS-CHOP) can cause Myxoid liposarcoma.[15]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000175197 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025408 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ 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.
  6. ↑ "Entrez Gene: DDIT3 DNA-damage-inducible transcript 3".
  7. ↑ 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.
  8. 1 2 3 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I (2009). "Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis". Journal of Cell Biology. 186 (6): 783–792. doi:10.1083/jcb.200904060. PMC 2753154. PMID 19752026.
  14. ↑ Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP, Ron D (2004). "CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum". Genes & Development. 18 (24): 3066–3077. doi:10.1101/gad.1250704. PMC 535917. PMID 15601821.
  15. ↑ 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. doi:10.1128/MCB.16.3.1157. 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.

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