Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival.

Details

Serval ID
serval:BIB_D7D4A7A31084
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival.
Journal
Blood
Author(s)
Goux D., Coudert J.D., Maurice D., Scarpellino L., Jeannet G., Piccolo S., Weston K., Huelsken J., Held W.
ISSN
0006-4971
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
106
Number
5
Pages
1726-1733
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Intrathymic T-cell maturation critically depends on the selective expansion of thymocytes expressing a functionally rearranged T-cell receptor (TCR) beta chain. In addition, TCR-independent signals also contribute to normal T-cell development. It is unclear whether and how signals from the 2 types of pathways are integrated. Here, we show that T-cell factor-1 (TCF-1), a nuclear effector of the canonical wingless/int (wnt)/catenin signaling pathway, ensures the survival of proliferating, pre-TCR(+) thymocytes. The survival of pre-TCR(+) thymocytes requires the presence of the N-terminal catenin-binding domain in TCF-1. This domain can bind the transcriptional coactivator beta-catenin and may also bind gamma-catenin (plakoglobin). However, in the absence of gamma-catenin, T-cell development is normal, supporting a role for beta-catenin. Signaling competent beta-catenin is present prior to and thus arises independently from pre-TCR signaling and does not substantially increase on pre-TCR signaling. In contrast, pre-TCR signaling significantly induces TCF-1 expression. This coincides with the activation of a wnt/catenin/TCF reporter transgene in vivo. Collectively, these data suggest that efficient TCF-dependent transcription requires that pre-TCR signaling induces TCF-1 expression, whereas wnt signals may provide the coactivator such as beta-catenin. The 2 pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage.
Keywords
Animals, Cell Cycle/drug effects, Cell Cycle/immunology, Cell Differentiation/drug effects, Cell Differentiation/immunology, Cell Survival/drug effects, Cell Survival/immunology, Cytoskeletal Proteins/pharmacology, DNA-Binding Proteins/deficiency, DNA-Binding Proteins/immunology, Desmoplakins, Homeodomain Proteins/immunology, Intercellular Signaling Peptides and Proteins/immunology, Lymphoid Enhancer-Binding Factor 1, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell/immunology, Signal Transduction/immunology, Structure-Activity Relationship, T Cell Transcription Factor 1, T-Lymphocytes/immunology, Thymus Gland/cytology, Thymus Gland/immunology, Transcription Factors/deficiency, Transcription Factors/immunology, Wnt Proteins, gamma Catenin
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2008 15:24
Last modification date
20/08/2019 15:57
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