| General information | Literature | Expression | Regulation | Mutation | Interaction |
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Basic Information |
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|---|---|
Gene ID | 1647 |
Name | GADD45A |
Synonymous | DDIT1|GADD45;growth arrest and DNA-damage-inducible, alpha;GADD45A;growth arrest and DNA-damage-inducible, alpha |
Definition | DDIT-1|DNA damage-inducible transcript 1 protein|DNA damage-inducible transcript-1|DNA-damage-inducible transcript 1|growth arrest and DNA damage-inducible protein GADD45 alpha|growth arrest and DNA-damage-inducible 45 alpha |
Position | 1p31.2 |
Gene type | protein-coding |
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Title |
Abstract |
| G2/M arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer. | 1,25-Dihydroxyvitamin D3 suppresses the growth of multiple human cancer cell lines by inhibiting cell cycle progression and inducing cell death. The present study showed that 1,25-dihydroxyvitamin D3 causes cell cycle arrest at the G2/M transition through p53-independent induction of GADD45 in ovarian cancer cells. Detailed analyses have established GADD45 as a primary target gene for 1,25-dihydroxyvitamin D3. A DR3-type vitamin D response element was identified in the fourth exon of GADD45 that forms a complex with the vitamin D receptor.retinoid X receptor heterodimer in electrophoresis mobility shift assays and mediates the dose-dependent induction of luciferase activity by 1,25-dihydroxyvitamin D3 in reporter assays. Chromatin immunoprecipitation assays have shown that the vitamin D receptor is recruited in a ligand-dependent manner to the exonic enhancer but not to the GADD45 promoter regions. In ovarian cancer cells expressing GADD45 antisense cDNA or GADD45-null mouse embryo fibroblasts, 1,25-dihydroxyvitamin D3 failed to induce G2/M arrest. Taken together, these results identify GADD45 as an important mediator for the tumor-suppressing activity of 1,25-dihydroxyvitamin D3 in human ovarian cancer cells. |