Regulation of NF-κB-dependent lymphocyte activation and development by paracaspase
Regulation of NF-κB-dependent lymphocyte activation and development by paracaspase
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DOI：
10.1126/science.1090769
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发表时间：
2003-11-28
期刊：
影响因子：
56.9
通讯作者：
Dixit, VM
中科院分区：
文献类型：
--
作者：
Ruefli-Brasse, AA;French, DM;Dixit, VM
副半胱天冬酶 (MALT1) 是进化上保守的半胱天冬酶样蛋白超家族的成员，已被证明在体外与蛋白 Bcl10 结合并共定位，并且由于这种关联，被认为参与抗原诱导核因子 kappaB (NF-kappaB) 激活的 CARMA1-Bcl10 途径。我们证明，副半胱天冬酶缺陷型小鼠的原代 T 和 B 淋巴细胞在抗原受体诱导的 NF-κB 激活、细胞因子产生和增殖方面存在缺陷。 Paracaspase 作用于 Bcl10 下游，诱导 NF-kappaB 激活，并且是 B 细胞正常发育所必需的，这表明 paracaspase 提供了 Bcl10 和 IkappaB 激酶复合物激活之间缺失的联系。
Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF-kappaB) activation. We demonstrate that primary T and B lymphocytes from para-caspase-deficient mice are defective in antigen-receptor-induced NF-kappaB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex.