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Alternative titles; symbolsNITRIC OXIDE-INDUCIBLE GENE; NOXINCHROMOSOME 11 OPEN READING FRAME 82; C11ORF82HGNC Approved Gene Symbol: DDIASCytogenetic location: 1...

Alternative titles; symbols


HGNC Approved Gene Symbol: DDIAS

Cytogenetic location: 11q14.1 Genomic coordinates (GRCh38): 11:82,901,734-82,934,658 (from NCBI)

▼ Description
DDIAS is an antiapoptotic protein activated by various stress stimuli (Nakaya et al., 2007).

▼ Cloning and Expression
Nakaya et al. (2007) cloned mouse Ddias, which they called noxin. The deduced 898-amino acid protein has a calculated molecular mass of 100 kD. Ddias is rich in serines and has 2 predicted nuclear localization domains near the N and C termini. It also has part of a C3HC4-type zinc finger domain in its N-terminal region. Northern blot analysis of mouse tissues detected Ddias expression predominantly in testis, but also in spleen and heart. Quantitative PCR also showed expression in mouse bone marrow, brain, lung, liver, and kidney. In situ hybridization, immunocytochemistry, and Western blot analysis confirmed strong expression in mouse testis. Ddias was highly expressed in primary spermatocytes and, to a lesser extent, in round spermatids. In spermatocytes, Ddias localized to the periphery of the nucleus, in a structure that may correspond to the centrosome, the Golgi body, or the XY body. Exogenic expression of Ddias in NIH-3T3 cells showed nuclear and cytoplasmic localization of Ddias. When in nucleus, Ddias was expressed in subnuclear particles in euchromatic regions.

Won et al. (2014) reported that human DDIAS contains 998 amino acids and has an N-terminal DNA-binding domain (DBD) C. Human and mouse DDIAS share significant homology in the N-terminal region containing DBD C, but they share less homology throughout the rest of the sequence, despite several conserved sequences. RT-PCR of human tissues showed DDIAS expression in testis, pancreas, and prostate, with weaker expression in lung, stomach, thymus, colon and heart. RT-PCR and mRNA in situ hybridization revealed strong expression of DDIAS in human colorectal and lung cancer tissues.

▼ Gene Structure
Won et al. (2014) reported that the human DDIAS gene has 6 exons. The translation start site is in exon 3.

▼ Mapping
Nakaya et al. (2007) reported that the DDIAS gene maps to human chromosome 11 and mouse chromosome 7.

Gross (2018) mapped the DDIAS gene to chromosome 11q14.1 based on an alignment of the DDIAS sequence (GenBank BC039268) with the genomic sequence (GRCh38).

▼ Gene Function
Nakaya et al. (2007) found that expression of mouse Ddias was induced by a wide range of stress stimuli, including nitric oxide. Stress-induced Ddias expression was p53 (TP53; 191170) dependent and controlled by the cell cycle, as Ddias expression was associated with G2/M phase in mouse cells. Ddias expression induced cell-cycle arrest in mice in a p53-independent manner. Using Ddias-knockout and -downregulated mouse cells, the authors showed that Ddias acted as an antiapoptotic factor whose absence increased cell death under normal and stress conditions.

Won et al. (2014) showed that human DDIAS expression was associated with S phase of the cell cycle and induced by ultraviolet exposure in both normal lung and lung cancer cells. Knockdown of DDIAS inhibited growth of human colorectal and lung cancer cells, but not normal human cells. Knockdown of DDIAS caused DNA damage and induced apoptosis of A549 nonsmall cell lung cancer cells through activation of p38 MAPK (MAPK14; 600289)/p53, which could be suppressed by overexpression of human DDIAS. Knockdown of human DDIAS combined with treatment with DNA-damaging agents enhanced apoptosis of A549 cells, as DDIAS knockdown sensitized cells to the DNA-damaging agents. In addition, knockdown of human DDIAS significantly suppressed growth of A549 tumor xenografts.

Using overexpression and knockdown experiments, Im et al. (2016) found that expression of DDIAS was upregulated in human cancer cells in response to EGF (131530) via ERK5 (602521), an essential mediator of EGF signaling, and MEF2B (600661), a downstream target of ERK5. MEF2B was recruited to an MEF2-binding site in the promoter of DDIAS following treatment with EGF. The authors identified DDIAS as a critical mediator of EGF-induced beta-catenin (CTNNB1; 116806) signaling, as DDIAS activated beta-catenin-mediated HeLa cell invasion by increasing beta-catenin expression at the posttranslational level in response to EGF.

▼ Animal Model
Nakaya et al. (2007) found that homozygous Ddias-knockout mice were viable and fertile with no detectable abnormalities other than enlarged heart. The number of round spermatids in testis was a significantly decreased in Ddias-knockout mice. Tests of a wide range of hematopoiesis-related parameters revealed only a few significant differences between wildtype and knockout mice.

Tags: 11q14.1