Menon Suchithra, Chi Hongbo, Zhang Huiyong, Deng Xing Wang, Flavell Richard A, Wei Ning
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA.
Nat Immunol. 2007 Nov;8(11):1236-45. doi: 10.1038/ni1514. Epub 2007 Sep 30.
Engagement of antigen receptors triggers the proliferation and functional activation of lymphocytes. Here we report that T cell homeostasis and antigen-induced responses require the COP9 signalosome (CSN), a regulator of the ubiquitin-proteasome system. Conditional deletion of the CSN subunit Csn8 in peripheral T lymphocytes disrupted formation of the CSN complex, reduced T cell survival and proliferation in vivo and impaired antigen-induced production of interleukin 2. Moreover, Csn8-deficient T cells showed defective entry into the cell cycle from the G0 quiescent state. This phenotype was associated with a lack of signal-induced expression of cell cycle-related genes, including G1 cyclins and cyclin-dependent kinases, and with excessive induction of p21(Cip1). Our data define a CSN-dependent pathway of transcriptional control that is essential for antigen-induced initiation of T cell proliferation.
抗原受体的激活会触发淋巴细胞的增殖和功能活化。我们在此报告，T细胞稳态和抗原诱导的反应需要COP9信号体（CSN），这是一种泛素-蛋白酶体系统的调节因子。外周T淋巴细胞中CSN亚基Csn8的条件性缺失破坏了CSN复合物的形成，降低了体内T细胞的存活和增殖，并损害了抗原诱导的白细胞介素2的产生。此外，缺乏Csn8的T细胞从G0静止状态进入细胞周期存在缺陷。这种表型与细胞周期相关基因（包括G1期细胞周期蛋白和细胞周期蛋白依赖性激酶）的信号诱导表达缺失以及p21（Cip1）的过度诱导有关。我们的数据定义了一条依赖CSN的转录控制途径，该途径对抗原诱导的T细胞增殖启动至关重要。
