GADD153 (Growth arrest and DNA damage-inducible 153; DNA-damage inducible transcript 3;) is a small nuclear protein that is capable of dimerizing with transcription factors C/EBP alpha and beta. Once dimerized, this complex inhibits the normal binding and function of C/EBP to classical binding sites. Inversely, the C/EBP GADD153 dimer gains binding activity to other non classical C/EBP stress related targets. Under normal cellular conditions this protein is not expressed in detectable levels, but is highly unregulated during times of cellular/ER stress. Examples of GADD153 inducing stress include: treatment with tunicamycin, nutrient starvation and reducing agents that interfere with the calcium flux across the ER membrane.
Function:
Inhibits the DNA-binding activity of C/EBP and LAP by forming heterodimers that cannot bind DNA.
Subunit:
Heterodimer. Interacts with TCF7L2/TCF4, EP300/P300, HDAC1, HDAC5 and HDAC6. Interacts with TRIB3 which blocks its association with EP300/P300. Interacts with FOXO3, CEBPB and ATF4.
Subcellular Location:
Cytoplasm. Nucleus. Note=Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.
Post-translational modifications:
Ubiquitinated, leading to its degradation by the proteasome.
Phosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity (By similarity).
DISEASE:
Note=A chromosomal aberration involving DDIT3 is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with FUS.
Similarity:
Belongs to the bZIP family.
Contains 1 bZIP domain.
SWISS:
P35638
Gene ID:
1649
Database links:
Entrez Gene: 1649 Human
Entrez Gene: 13198 Mouse
Entrez Gene: 29467 Rat
Entrez Gene: 398615 Xenopus laevis
Omim: 126337 Human
SwissProt: P35638 Human
SwissProt: P35639 Mouse
SwissProt: Q62857 Rat
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Tissue/cell: human lung carcinoma; 4% Paraformaldehyde-fixed and paraffin-embedded;
Antigen retrieval: citrate buffer ( 0.01M, pH 6.0 ), Boiling bathing for 15min; Block endogenous peroxidase by 3% Hydrogen peroxide for 30min; Blocking buffer (normal goat serum,SLC0005) at 37℃ for 20 min;
Incubation: Anti-GADD153 Polyclonal Antibody, Unconjugated(SL8875R) 1:200, overnight at 4°C, followed by conjugation to the secondary antibody(SP-0023) and DAB(SLC0010) staining
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