T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-κB inhibitor A20
T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-κB inhibitor A20
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DOI：
10.1038/ni1561
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发表时间：
2008-03-01
影响因子：
30.5
通讯作者：
Beyaert, Rudi
中科院分区：
文献类型：
--
作者：
Coornaert, Beatrice;Baens, Mathijs;Beyaert, Rudi
paracaspase MALT 1介导T细胞抗原受体诱导的信号传导至转录因子NF-κ B，并且是T细胞活化和增殖所必需的。MALT 1的表达增强或凋亡抑制剂API 2和MALT 1的融合蛋白的异常表达与粘膜相关淋巴组织淋巴瘤有关。尽管存在半胱天冬酶样结构域，MALT 1蛋白水解活性尚未得到证实。在这里，我们表明，T细胞抗原受体刺激诱导招聘的NF-κ B抑制剂A20到一个复杂的MALT 1和衔接蛋白Bcl-10，导致MALT 1介导的处理A20。API 2-MALT 1表达同样导致A20的切割。MALT 1在精氨酸439后切割人A20并损害其NF-κ B抑制功能。我们的研究确定了A20作为MALT 1的底物，并强调了MALT 1蛋白水解活性在T细胞抗原受体信号转导的“微调”中的重要性。
The paracaspase MALT1 mediates T cell antigen receptor-induced signaling to the transcription factor NF-kappa B and is indispensable for T cell activation and proliferation. Enhanced expression of MALT1 or aberrant expression of a fusion protein of the apoptosis inhibitor API2 and MALT1 has been linked to mucosa-associated lymphoid tissue lymphoma. Despite the presence of a caspase-like domain, MALT1 proteolytic activity has not yet been demonstrated. Here we show that T cell antigen receptor stimulation induced recruitment of the NF-kappa B inhibitor A20 into a complex of MALT1 and the adaptor protein Bcl-10, leading to MALT1-mediated processing of A20. API2-MALT1 expression likewise resulted in cleavage of A20. MALT1 cleaved human A20 after arginine 439 and impaired its NF-kappa B-inhibitory function. Our studies identify A20 as a substrate of MALT1 and emphasize the importance of MALT1 proteolytic activity in the 'fine tuning' of T cell antigen receptor signaling.