Stabilization of β-Catenin Directs HEB to Limit Thymic Selection.

ABSTRACT: Activation of β-catenin in CD4+CD8+ double-positive (DP) thymocytes halts development before the thymic selection stage and predisposes to transformation. Leukemogenesis, but not the developmental block, depends on TCF-1, β-catenin's DNA-binding partner. In this study, we show that β-catenin activation directs the DNA-binding protein HEB to block DP thymocyte development. Conditional loss of HEB in DP thymocytes with stabilized β-catenin restores the frequencies of postselection TCRβhi/CCR7+ and TCRβhi/CD69+ DPs and their cell-cycle profile. This recovery is associated with significant reversal of β-catenin-induced expression changes, particularly those related to the CD69+ DP cell signature and to cell-cycle pathways. Stabilizing β-catenin in DP thymocytes directs HEB binding to ≈11,000 n

SUBMITTER: Tousinas G 

PROVIDER: S-EPMC11333165 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature