| First Author | Newton K | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 5 | Pages | 931-41 |
| PubMed ID | 10698935 | Mgi Jnum | J:60895 |
| Mgi Id | MGI:1354063 | Doi | 10.1093/emboj/19.5.931 |
| Citation | Newton K, et al. (2000) FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. EMBO J 19(5):931-41 |
| abstractText | Productive rearrangement of the T-cell receptor (TCR) beta gene and signalling through the pre-TCR-CD3 complex are required for survival, proliferation and differentiation of T-cell progenitors (pro-T cells). Here we identify a role for death receptor signalling in early T-cell development using a dominant-negative mutant of the death receptor signal transducer FADD/MORT1 (FADD-DN). In rag-1(-/-) thymocytes, which are defective in antigen receptor gene rearrangement, FADD-DN bypassed the requirement for pre-TCR signalling, promoting pro-T-cell survival and differentiation to the more mature pre-T stage. Surprisingly, differentiation was not accompanied by the proliferation that occurs normally during transition to the pre-T stage. Consistent with a role for FADD/MORT1 in this cell division, FADD-DN rag-1(-/-) pro-T cells failed to proliferate in response to CD3epsilon ligation. Concomitant signalling through the pre-TCR and death receptors appears to trigger pro-T cell survival, proliferation and differentiation, whereas death receptor signalling in thymocytes that lack a pre-TCR induces apoptosis. Later in life all FADD-DN rag-1(-/-) mice developed thymic lymphoma, indicating that FADD/MORT1 can act as a tumour suppressor. |
