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DDIT3 (DNA damage inducible transcript 3)

Written2004-07Pedro A Pérez-Mancera, Isidro Sánchez-Garcìa
Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain

(Note : for Links provided by Atlas : click)

Identity

Other aliasCHOP (C/EBP homologous protein)
CHOP-10 (C/EBP homologous protein 10)
GADD153 (Growth arrest and DNA damage inducible gene 153)
C/EBP zeta (CCAAT/enhancer binding protein zeta)
LocusID (NCBI) 1649
Atlas_Id 80
Location 12q13.3  [Link to chromosome band 12q13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DDIT3 (12q13.3) / ATF2 (2q31.1)DDIT3 (12q13.3) / DDIT3 (12q13.3)DDIT3 (12q13.3) / EWSR1 (22q12.2)
DDIT3 (12q13.3) / FUS (16p11.2)DDIT3 (12q13.3) / GLI1 (12q13.3)EWSR1 (22q12.2) / DDIT3 (12q13.3)
FUS (16p11.2) / DDIT3 (12q13.3)

DNA/RNA

Description 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.
Transcription Transcript lenght: 1,1 Kb.

Protein

 
Description 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.
Expression DDIT3 is expressed ubiquitously. It is usually expressed at undetectable levels and its expression is induced by cellular stress.
Localisation Nuclear.
Function 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.
Homology 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.

Mutations

Germinal 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

Note
Note 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.
 
  
  
Entity t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3.
Disease Myxoid liposarcoma (MLS).
Hybrid/Mutated 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.
Oncogenesis 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 t(12;22)(q13;q12) chromosomal translocation. It produces the fusion protein EWS/DDIT3.
Disease Myxoid liposarcoma (MLS).
Hybrid/Mutated 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.
  

Breakpoints

 

Bibliography

-
 
Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).
Aman P, Ron D, Mandahl N, Fioretos T, Heim S, Arheden K, Willén H, Rydholm A, Mitelman F
Genes, chromosomes & cancer. 1992 ; 5 (4) : 278-285.
PMID 1283316
 
CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest.
Barone MV, Crozat A, Tabaee A, Philipson L, Ron D
Genes & development. 1994 ; 8 (4) : 453-464.
PMID 8125258
 
Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).
Batchvarova N, Wang XZ, Ron D
The EMBO journal. 1995 ; 14 (19) : 4654-4661.
PMID 7588595
 
Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
Cao Z, Umek RM, McKnight SL
Genes & development. 1991 ; 5 (9) : 1538-1552.
PMID 1840554
 
Regulation of the C/EBP-related gene gadd153 by glucose deprivation.
Carlson SG, Fawcett TW, Bartlett JD, Bernier M, Holbrook NJ
Molecular and cellular biology. 1993 ; 13 (8) : 4736-4744.
PMID 8336711
 
Regulated expression and functional role of the transcription factor CHOP (GADD153) in erythroid growth and differentiation.
Coutts M, Cui K, Davis KL, Keutzer JC, Sytkowski AJ
Blood. 1999 ; 93 (10) : 3369-3378.
PMID 10233889
 
Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.
Crozat A, Aman P, Mandahl N, Ron D
Nature. 1993 ; 363 (6430) : 640-644.
PMID 8510758
 
Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis.
Cui K, Coutts M, Stahl J, Sytkowski AJ
The Journal of biological chemistry. 2000 ; 275 (11) : 7591-7596.
PMID 10713066
 
The role of C/EBP genes in adipocyte differentiation.
Darlington GJ, Ross SE, MacDougald OA
The Journal of biological chemistry. 1998 ; 273 (46) : 30057-30060.
PMID 9804754
 
Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents.
Fornace AJ Jr, Nebert DW, Hollander MC, Luethy JD, Papathanasiou M, Fargnoli J, Holbrook NJ
Molecular and cellular biology. 1989 ; 9 (10) : 4196-4203.
PMID 2573827
 
A novel type of EWS-CHOP fusion gene in two cases of myxoid liposarcoma.
Hosaka T, Nakashima Y, Kusuzaki K, Murata H, Nakayama T, Nakamata T, Aoyama T, Okamoto T, Nishijo K, Araki N, Tsuboyama T, Nakamura T, Toguchida J
The Journal of molecular diagnostics : JMD. 2002 ; 4 (3) : 164-171.
PMID 12169678
 
Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.
Knight JC, Renwick PJ, Cin PD, Van den Berghe H, Fletcher CD
Cancer research. 1995 ; 55 (1) : 24-27.
PMID 7805034
 
Biological role of the CCAAT/enhancer-binding protein family of transcription factors.
Lekstrom-Himes J, Xanthopoulos KG
The Journal of biological chemistry. 1998 ; 273 (44) : 28545-28548.
PMID 9786841
 
Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.
Pérez-Mancera PA, Pérez-Losada J, Sánchez-Martín M, Rodríguez-García MA, Flores T, Battaner E, Gutiérrez-Adán A, Pintado B, Sánchez-García I
Oncogene. 2002 ; 21 (11) : 1679-1684.
PMID 11896599
 
A novel FUS/CHOP chimera in myxoid liposarcoma.
Panagopoulos I, Mertens F, Isaksson M, Mandahl N
Biochemical and biophysical research communications. 2000 ; 279 (3) : 838-845.
PMID 11162437
 
Isolation, characterization and chromosomal localization of the human GADD153 gene.
Park JS, Luethy JD, Wang MG, Fargnoli J, Fornace AJ Jr, McBride OW, Holbrook NJ
Gene. 1992 ; 116 (2) : 259-267.
PMID 1339368
 
Gadd45 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, Calderwood SK
Cancer research. 1992 ; 52 (13) : 3814-3817.
PMID 1617653
 
Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.
Rabbitts TH, Forster A, Larson R, Nathan P
Nature genetics. 1993 ; 4 (2) : 175-180.
PMID 7503811
 
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.
Ron D, Habener JF
Genes & development. 1992 ; 6 (3) : 439-453.
PMID 1547942
 
Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element.
Ubeda M, Wang XZ, Zinszner H, Wu I, Habener JF, Ron D
Molecular and cellular biology. 1996 ; 16 (4) : 1479-1489.
PMID 8657121
 
Identification of novel stress-induced genes downstream of chop.
Wang XZ, Kuroda M, Sok J, Batchvarova N, Kimmel R, Chung P, Zinszner H, Ron D
The EMBO journal. 1998 ; 17 (13) : 3619-3630.
PMID 9649432
 
Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153).
Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ, Boorstein R, Kreibich G, Hendershot LM, Ron D
Molecular and cellular biology. 1996 ; 16 (8) : 4273-4280.
PMID 8754828
 
Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.
Yeh WC, Cao Z, Classon M, McKnight SL
Genes & development. 1995 ; 9 (2) : 168-181.
PMID 7531665
 
CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.
Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D
Genes & development. 1998 ; 12 (7) : 982-995.
PMID 9531536
 

Citation

This paper should be referenced as such :
Pérez-Mancera, PA ; Sanchez-Garcia, I
DDIT3 (DNA damage inducible transcript 3)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):232-235.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DDIT3ID80.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(8;14)(q11;q32) IGH/CEBPD
t(14;14)(q11;q32) CEBPE/IGH::inv(14)(q11q32) CEBPE/IGH
t(14;19)(q32;q13) IGH/CEBPA
t(14;20)(q32;q13) IGH/CEBPB


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ]
  Soft Tissues: Angiomatoid fibrous histiocytoma
Nervous System: Glioma: an overview
Soft Tissues: Low grade fibromyxoid sarcoma
Soft Tissues: Liposarcoma: Myxoid liposarcoma
Soft tissue tumors: an overview
DDIT3/GLI1 (12q13)


External links

Nomenclature
Cards
AtlasDDIT3ID80.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)1649
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:33:29 CEST 2018

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