| First Author | Jung H | Year | 2013 |
| Journal | Cell Metab | Volume | 18 |
| Issue | 1 | Pages | 75-85 |
| PubMed ID | 23823478 | Mgi Jnum | J:199235 |
| Mgi Id | MGI:5501357 | Doi | 10.1016/j.cmet.2013.06.002 |
| Citation | Jung H, et al. (2013) TXNIP Maintains the Hematopoietic Cell Pool by Switching the Function of p53 under Oxidative Stress. Cell Metab 18(1):75-85 |
| abstractText | Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip(-/-) old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. Loss of TXNIP led to a dramatic reduction of mouse survival under oxidative stress. TXNIP directly regulated p53 protein by interfering with p53- mouse double minute 2 (MDM2) interactions and increasing p53 transcriptional activity. Txnip(-/-) mice showed downregulation of the antioxidant genes induced by p53. Introduction of TXNIP or p53 into Txnip(-/-) bone marrow cells rescued the HSC frequency and greatly increased survival in mice following oxidative stress. Overall, these data indicate that TXNIP is a regulator of p53 and plays a pivotal role in the maintenance of the hematopoietic cells by regulating intracellular ROS during oxidative stress. |
