Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity
Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity
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DOI：
10.1038/ni.1649
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发表时间：
2008-10-01
影响因子：
30.5
通讯作者：
Yasutomo, Koji
中科院分区：
文献类型：
--
作者：
Maekawa, Yoichi;Minato, Yoshiaki;Yasutomo, Koji
CD8(+)T细胞获得细胞毒效应功能是控制细胞内感染和肿瘤侵袭的关键。然而，CD8(+)细胞毒性T淋巴细胞的分化需要哪些信号通路，目前尚不清楚。我们在这里展示了Notch2缺陷的T细胞已经阻碍了向细胞毒性T细胞的分化。此外，Notch配体Delta-like 1低表达的树突状细胞诱导细胞毒性T淋巴细胞分化的效率较低。我们发现Notch2的胞内结构域与转录因子CREB1的磷酸化形式相互作用，这些蛋白共同结合转录辅助激活因子p300，在编码颗粒酶B的基因启动子上形成一个复合体。我们的结果表明，高度调控的、动态的T细胞毒性控制依赖于Notch2和CREB1信号的整合。
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.