| First Author | Tanaka T | Year | 2018 |
| Journal | Adv Biol Regul | Volume | 67 |
| Pages | 93-100 | PubMed ID | 29079355 |
| Mgi Jnum | J:342892 | Mgi Id | MGI:6883300 |
| Doi | 10.1016/j.jbior.2017.09.010 | Citation | Tanaka T, et al. (2018) DGKzeta ablation engenders upregulation of p53 level in the spleen upon whole-body ionizing radiation. Adv Biol Regul 67:93-100 |
| abstractText | The tumor suppressor gene product p53, which coordinates the cellular response to various stresses, is subject to tight regulation by a complex network of signal transduction. The DGK family metabolizes lipidic second messenger diacylglycerol to produce phosphatidic acid. Our earlier studies showed that one isozyme, DGKzeta, is involved in the regulatory mechanism of p53. In a cellular model of doxorubicin-induced DNA damage, overexpression of wild-type DGKzeta suppresses p53 protein induction and reduces apoptosis, whereas knockdown of DGKzeta upregulates p53 protein level and promotes apoptosis. Further examination reveals that DGKzeta facilitates p53 degradation via ubiquitin-proteasome system in the cytoplasm. However, it remains undetermined whether the regulatory mechanism of DGKzeta on p53 function found in cell-based experiments is also functional at the animal level. This study was conducted to elucidate this point using an experiment with DGKzeta-KO mice under DNA damage induced by whole-body ionizing radiation. Our results reveal that p53 protein is induced robustly in the spleen of DGKzeta-KO mice upon exposure to ionizing radiation, thereby promoting apoptosis in this organ. Taken together, the results demonstrate that DGKzeta plays a sentinel role in p53 expression at the cellular and organismal levels after DNA damaging stress conditions. |
