| First Author | Patel SP | Year | 2017 |
| Journal | Cell Mol Life Sci | Volume | 74 |
| Issue | 8 | Pages | 1553-1566 |
| PubMed ID | 27915416 | Mgi Jnum | J:240638 |
| Mgi Id | MGI:5888825 | Doi | 10.1007/s00018-016-2427-3 |
| Citation | Patel SP, et al. (2017) Opposing effects on the cell cycle of T lymphocytes by Fbxo7 via Cdk6 and p27. Cell Mol Life Sci 74(8):1553-1566 |
| abstractText | G1 phase cell cycle proteins, such as cyclin-dependent kinase 6 (Cdk6) and its activating partners, the D-type cyclins, are important regulators of T-cell development and function. An F-box protein, called F-box only protein 7 (Fbxo7), acts as a cell cycle regulator by enhancing cyclin D-Cdk6 complex formation and stabilising levels of p27, a cyclin-dependent kinase inhibitor. We generated a murine model of reduced Fbxo7 expression to test its physiological role in multiple tissues and found that these mice displayed a pronounced thymic hypoplasia. Further analysis revealed that Fbxo7 differentially affected proliferation and apoptosis of thymocytes at various stages of differentiation in the thymus and also mature T-cell function and proliferation in the periphery. Paradoxically, Fbxo7-deficient immature thymocytes failed to undergo expansion in the thymus due to a lack of Cdk6 activity, while mature T cells showed enhanced proliferative capacity upon T-cell receptor engagement due to reduced p27 levels. Our studies reveal differential cell cycle regulation by Fbxo7 at different stages in T-cell development. |
