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Publication : Cutting Edge: β-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions.

First Author  Xu Z Year  2017
Journal  J Immunol Volume  198
Issue  9 Pages  3404-3409
PubMed ID  28348272 Mgi Jnum  J:247679
Mgi Id  MGI:5925627 Doi  10.4049/jimmunol.1602139
Citation  Xu Z, et al. (2017) Cutting Edge: beta-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions. J Immunol 198(9):3404-3409
abstractText  T cell factor 1 (Tcf1) is essential for T cell development; however, it remains controversial whether beta-catenin, a known coactivator of Tcf1, has a role. Tcf1 is expressed in multiple isoforms in T lineage cells, with the long isoforms interacting with beta-catenin through an N-terminal domain. In this study, we specifically ablated Tcf1 long isoforms in mice (p45-/-mice) to abrogate beta-catenin interaction. Although thymic cellularity was diminished in p45-/- mice, transition of thymocytes through the maturation stages was unaffected, with no overt signs of developmental blocks. p45-/- thymocytes showed increased apoptosis and alterations in transcriptome, but these changes were substantially more modest than in thymocytes lacking all Tcf1 isoforms. These data indicate that Tcf1-beta-catenin interaction is necessary for promoting thymocyte survival to maintain thymic output. Rather than being dominant-negative regulators, Tcf1 short isoforms are adequate in supporting developing thymocytes to traverse through maturation steps and in regulating the expression of most Tcf1 target genes.
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