| First Author | Iwaihara Y | Year | 2015 |
| Journal | Anticancer Res | Volume | 35 |
| Issue | 8 | Pages | 4419-23 |
| PubMed ID | 26168481 | Mgi Jnum | J:323779 |
| Mgi Id | MGI:6756881 | Citation | Iwaihara Y, et al. (2015) Marked Reduction in FoxO1 Protein by its Enhanced Proteasomal Degradation in Zfat-deficient Peripheral T-Cells. Anticancer Res 35(8):4419-23 |
| abstractText | BACKGROUND: Zfat is a nuclear protein that harbours putative DNA-binding domains. T-cell specific deletion of Zfat in Zfat(f/f)-CD4Cre mice yields a significant decrease in the number of peripheral T-cells with a lower surface expression of interleukin-7 receptor-alpha (IL-7Ralpha). However, the molecular mechanism by which Zfat controls IL-7Ralpha expression remains unknown. MATERIALS AND METHODS: Expression levels of the molecules involved in IL-7Ralpha expression were determined by immunoblotting. RESULTS: Zfat-deficient peripheral T-cells showed a marked reduction in the FoxO1 protein that regulates IL-7Ralpha expression; however, the FoxO1 mRNA expression level was not affected by Zfat-deficiency. Furthermore, treatment of Zfat-deficient T-cells with a proteasome inhibitor, epoxomicin, restored FoxO1 expression levels, indicating that the loss of Zfat enhanced the proteasomal degradation of the FoxO1 protein. CONCLUSION: These results suggest that Zfat is required for peripheral T-cell homeostasis through IL-7Ralpha expression by controlling the FoxO1 protein. |
