FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor
- Author(s)
- Newton, K; Harris, AW; Strasser, A;
- Details
- Publication Year 2000-03-01,Volume 19,Issue #5,Page 931-941
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- Abstract
- 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 CD3 epsilon 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.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- CELL RECEPTOR-BETA; MATURE T-LYMPHOCYTES; DEVELOPMENT IN-VIVO; DEFICIENT MICE; SCID MICE; V(D)J RECOMBINATION; CD4(+)CD8(+) THYMOCYTES; DEATH DOMAIN; FAS ANTIGEN; DNA-DAMAGE
- Publisher's Version
- https://doi.org/10.1093/emboj/19.5.931
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-03-01 12:00:00