Notch-Regulated Ankyrin-Repeat Protein Inhibits Notch1 Signaling: Multiple Notch1 Signaling Pathways Involved In T Cell Development | Zendy

Theodore J. Yun | Zendy; Michael J. Bevan | Zendy

Open Access

Notch-Regulated Ankyrin-Repeat Protein Inhibits Notch1 Signaling: Multiple Notch1 Signaling Pathways Involved In T Cell Development

Author(s) -

Theodore J. Yun,

Michael J. Bevan

Publication year - 2003

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.170.12.5834

Subject(s) - notch signaling pathway , thymocyte , biology , microbiology and biotechnology , phenotype , haematopoiesis , hes3 signaling axis , signal transduction , t cell , cellular differentiation , ankyrin repeat , stem cell , gene , immunology , genetics , immune system

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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