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- Title
Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity.
- Authors
Maekawa, Yoichi; Minato, Yoshiaki; Ishifune, Chieko; Kurihara, Takeshi; Kitamura, Akiko; Kojima, Hidefumi; Yagita, Hideo; Sakata-Yanagimoto, Mamiko; Saito, Toshiki; Taniuchi, Ichiro; Chiba, Shigeru; Sone, Saburo; Yasutomo, Koji
- Abstract
The acquisition of cytotoxic effector function by CD8+ T cells is crucial for the control of intracellular infection and tumor invasion. However, it remains unclear which signaling pathways are required for the differentiation of CD8+ cytotoxic T lymphocytes. We show here that Notch2-deficient T cells had impaired differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with lower expression of the Notch ligand Delta-like 1 induced the differentiation of cytotoxic T lymphocytes less efficiently. We found that the intracellular domain of Notch2 interacted with a phosphorylated form of the transcription factor CREB1, and together these proteins bound the transcriptional coactivator p300 to form a complex on the promoter of the gene encoding granzyme B. Our results suggest that the highly regulated, dynamic control of T cell cytotoxicity depends on the integration of Notch2 and CREB1 signals.
- Publication
Nature Immunology, 2008, Vol 9, Issue 10, p1140
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1649