DDIT3 (DNA damage inducible transcript 3)

2004-07-01   Pedro A Pérez-Mancera , Isidro Sánchez-García 

Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain





The gene has 4 exons (94 bp, 48 bp, 167 bp and 586 bp). The start codon is in the exon 3. The total genomic sequence spanning the DDIT3 gene is approx. 3 Kb.


Transcript lenght: 1,1 Kb.


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169 amino acids, 29 Kda. DDIT3 contains a carboxy-terminal region (bZIP) formed by a DNA-binding basic domain and a leucine zipper dimerization domain.


DDIT3 is expressed ubiquitously. It is usually expressed at undetectable levels and its expression is induced by cellular stress.




DDIT3 does not form homodimers and it functions as a dominant negative C/EBP forming heterodimers with other C/EBP members and preventing their binding to C/EBP sequences in the DNA. DDIT3 is implicated in adipogenesis, erythropoiesis, in the induction of growth arrest and in the endoplasmic reticulum stress response.


DDIT3 belongs to the CCAAT/enhancer binding protein (C/EBP) family of transcription factors and it has been found to have high homology in hamster, rat and mouse.



In the mouse, germine mutation in the ddit3 gene produces a decrease in the programmed cell death induced by perturbation in the endoplasmic reticulum function. On the other hand, while DDIT3 inhibits adipogenesis in 3T3-L1 preadipocytes, transgenic mice expressing DDIT3 from a housekeeping promoter display normal adipogenesis.

Implicated in

The DDIT3 gene is implicated in two chromosomal translocations associated to the myxoid liposarcoma (MLS). These fusion proteins generated as a result of chromosomal rearragements are used to monitor diagnosis and treatment.
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Entity name
t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3.
Myxoid liposarcoma (MLS).
Hybrid gene
9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3.
The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter.
Entity name
t(12;22)(q13;q12) chromosomal translocation. It produces the fusion protein EWS/DDIT3.
Myxoid liposarcoma (MLS).
Hybrid gene
2 different types of fusions between the genes EWS and DDIT3 have been reported. The first one joins the exon 7 of EWS with the exon 2 of DDIT3, while the second one joins the exon 10 of EWS with the exon 2 of DDIT3.


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Pubmed IDLast YearTitleAuthors
12833161992Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).Aman P et al
81252581994CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest.Barone MV et al
75885951995Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).Batchvarova N et al
18405541991Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.Cao Z et al
83367111993Regulation of the C/EBP-related gene gadd153 by glucose deprivation.Carlson SG et al
102338891999Regulated expression and functional role of the transcription factor CHOP (GADD153) in erythroid growth and differentiation.Coutts M et al
85107581993Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.Crozat A et al
107130662000Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis.Cui K et al
98047541998The role of C/EBP genes in adipocyte differentiation.Darlington GJ et al
25738271989Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents.Fornace AJ Jr et al
121696782002A novel type of EWS-CHOP fusion gene in two cases of myxoid liposarcoma.Hosaka T et al
78050341995Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.Knight JC et al
97868411998Biological role of the CCAAT/enhancer-binding protein family of transcription factors.Lekstrom-Himes J et al
118965992002Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.Pérez-Mancera PA et al
111624372000A novel FUS/CHOP chimera in myxoid liposarcoma.Panagopoulos I et al
13393681992Isolation, characterization and chromosomal localization of the human GADD153 gene.Park JS et al
16176531992Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins.Price BD et al
75038111993Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.Rabbitts TH et al
15479421992CHOP, 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.Ron D et al
86571211996Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element.Ubeda M et al
96494321998Identification of novel stress-induced genes downstream of chop.Wang XZ et al
87548281996Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153).Wang XZ et al
75316651995Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.Yeh WC et al
95315361998CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.Zinszner H et al

Other Information

Locus ID:

NCBI: 1649
MIM: 126337
HGNC: 2726
Ensembl: ENSG00000175197


dbSNP: 1649
ClinVar: 1649
TCGA: ENSG00000175197


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
MAPK signaling pathwayKEGGhsa04010
Protein processing in endoplasmic reticulumKEGGko04141
Protein processing in endoplasmic reticulumKEGGhsa04141
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Metabolism of proteinsREACTOMER-HSA-392499
Unfolded Protein Response (UPR)REACTOMER-HSA-381119
ATF6 (ATF6-alpha) activates chaperonesREACTOMER-HSA-381033
ATF6 (ATF6-alpha) activates chaperone genesREACTOMER-HSA-381183
PERK regulates gene expressionREACTOMER-HSA-381042
ATF4 activates genesREACTOMER-HSA-380994

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
146851632004Roles of CHOP/GADD153 in endoplasmic reticulum stress.814
198553862009Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling.117
176868662007West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis.112
197237032010Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways.103
208761142010Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression.99
146309182004Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation.94
272118002016The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress.91
204308722010CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis.72
118050882002Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP.66
189407922008C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene.61


Pedro A Pérez-Mancera ; Isidro Sánchez-García

DDIT3 (DNA damage inducible transcript 3)

Atlas Genet Cytogenet Oncol Haematol. 2004-07-01

Online version: http://atlasgeneticsoncology.org/gene/80/ddit3-(dna-damage-inducible-transcript-3)