Journal
JOURNAL OF IMMUNOLOGY
Volume 170, Issue 12, Pages 5834-5841Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.170.12.5834
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NIAID NIH HHS [R01 AI029802-11, AI29802] Funding Source: Medline
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We have characterized the function of Notch-regulated ankyrin-repeat protein (Nrarp) in mouse cell lines and in hematopoietic stem cells (HSCs). Nrarp overexpression is able to block Notch-induced activation of CBF-1. In AKR1010 thymoma cells, Nrarp overexpression blocks CBF-1-dependent transcriptional activation of Notch-responsive genes and inhibits phenotypic changes associated with. Notch activation. Enforced expression of Nrarp in mouse HSCs results in a profound block in T lineage commitment and progression through early stages of thymocyte maturation. In contrast, Deltex-1 overexpression in HSCs can also block T lineage commitment but not progression through the early double negative stages of thymocyte maturation. The different effects of Deltex-1 and Nrarp overexpression suggest that alternate Notch signaling pathways mediate T vs B lineage commitment and thymocyte maturation.
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