Download Gene Section DDIT3 (DNA damage inducible transcript 3) in Oncology and Haematology

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Gene Section
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DDIT3 (DNA damage inducible transcript 3)
Pedro 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 (PAPM, ISG)
Published in Atlas Database: July 2004
Online updated version: http://AtlasGeneticsOncology.org/Genes/DDIT3ID80.html
DOI: 10.4267/2042/38108
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2004 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Function
Other names: CHOP (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)
HGNC (Hugo): DDIT3
Location: 12q13.1-q13.2
DDIT3 does not form homodimers and it functions as a
dominant negative C/EBP forming hetero-dimers with
other C/EBP members and preventing their binding to
C/EBP sequences in the DNA. DDIT3 is implicated in
adipogenesis, erythro-poiesis, in the induction of
growth arrest and in the endoplasmic reticulum stress
response.
Homology
DNA/RNA
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.
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.
Mutations
Transcription
Germinal
Transcript lenght: 1,1 Kb.
169 amino acids, 29 Kda. DDIT3 contains a carboxyterminal region (bZIP) formed by a DNA-binding basic
domain and a leucine zipper dimerization domain.
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 preadipo-cytes, transgenic
mice expressing DDIT3 from a housekeeping promoter
display normal adipo-genesis.
Expression
Implicated in
Protein
Description
DDIT3 is expressed ubiquitously. It is usually
expressed at undetectable levels and its expression is
induced by cellular stress.
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.
Localisation
Nuclear.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
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DDIT3 (DNA damage inducible transcript 3)
Pérez-Mancera PA, Sánchez-Garcìa I
t(12;16)(q13;p11) chromosomal
translocation. It produces the fusion
protein FUS/DDIT3.
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.
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.
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This article should be referenced as such:
Pérez-Mancera PA, Sánchez-Garcìa I. DDIT3 (DNA damage
inducible transcript 3). Atlas Genet Cytogenet Oncol Haematol.
2004; 8(3):242-244.
Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl
N, Aman P. Characteristic sequence motifs at the breakpoints
of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in
myxoid liposarcoma and acute myeloid leukemia. Oncogene.
1997 Sep;15(11):1357-62
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
244