Proteolysis of NF-κB1 p105 is essential for T cell antigen receptor-induced proliferation
Proteolysis of NF-κB1 p105 is essential for T cell antigen receptor-induced proliferation
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DOI：
10.1038/ni.1685
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发表时间：
2009-01-01
影响因子：
30.5
通讯作者：
Ley, Steven C.
中科院分区：
文献类型：
--
作者：
Sriskantharajah, Srividya;Belich, Monica P.;Ley, Steven C.
为了研究由激酶IKK诱导的NF-κ B1 p105蛋白水解在转录因子NF-κ B活化中的重要性，我们产生了“Nfkb 1（SSAA/SSAA）”小鼠，其中IKK靶向的p105丝氨酸残基被丙氨酸取代。Nfkb 1（SSAA/SSAA）小鼠由于细胞自主缺陷，CD 4（+）调节和记忆T细胞要少得多。这些T细胞亚型需要通过T细胞抗原受体激活NF-κ B以产生它们，并且Nfkb 1（SSAA）突变导致在T细胞抗原受体刺激后CD 4（+）T细胞中NF-κ B的较少激活和CD 4（+）T细胞的增殖。Nfkb 1（SSAA）突变也阻断了CD 4（+）T细胞在初次抗体应答期间为野生型B细胞提供帮助的能力。因此IKK诱导的p105蛋白水解对于最佳的T细胞抗原受体诱导的NF-κ B活化和成熟的CD 4（+）T细胞功能是必不可少的。
To investigate the importance of proteolysis of NF-kappa B1 p105 induced by the kinase IKK in activation of the transcription factor NF-kappa B, we generated 'Nfkb1(SSAA/SSAA)' mice, in which the IKK-target serine residues of p105 were substituted with alanine. Nfkb1(SSAA/SSAA) mice had far fewer CD4(+) regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappa B by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappa B in CD4(+) T cells and proliferation of CD4(+) T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4(+) T cells to provide help to wild-type B cells during a primary antibody response. IKK-induced p105 proteolysis is therefore essential for optimal T cell antigen receptor-induced activation of NF-kappa B and mature CD4(+) T cell function.