Lynch Oonagh T, Gadina Massimo
Department of Micrbiology and Immunology, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
Mol Interv. 2004 Jun;4(3):144-6. doi: 10.112/4.3.3.
Signal transduction through the T cell receptor (TCR) and a costimulatory molecule, CD28, results in the stimulation of multiple signaling pathways, leading to the activation of several transcription factors including activator protein-1 (AP-1), nuclear factor of activated T cells (NF-AT), and nuclear factor kappa B (NF-kappaB). The molecular mechanisms by which NF-kappaB is activated by TCR-CD28 have only recently become known. New findings indicate that the adaptor molecules CARMA1 and Bcl10 are essential to the process. Additionally, a critical role for MALT1/paracaspase has been identified. MALT1, CARMA1, and Bcl10 form a tripartite protein complex, in which Bcl10 is thought to facilitate the oligomerization of MALT1 monomers. Overexpression of MALT1, as observed in a subset of lymphoma patients, leads to the potent activation of NF-kappaB, suggesting that MALT1 might stimulate (directly or indirectly) the kinase complex [IKK, inhibitor of NF-kappaB (IkappaB) kinase] responsible for activating cytoplasmic NF-kappaB for translocation into the nucleus. Moreover, the MALT1-CARMA1-Bcl10 complex is responsible for ubiquitination of NEMO, a step that appears to be critical for TCR-induced NF-kappaB activation but not for induction mediated by other stimuli such as TNF or IL-1.
通过T细胞受体（TCR）和共刺激分子CD28进行的信号转导会刺激多种信号通路，从而导致包括激活蛋白-1（AP-1）、活化T细胞核因子（NF-AT）和核因子κB（NF-κB）在内的多种转录因子被激活。TCR-CD28激活NF-κB的分子机制直到最近才为人所知。新的研究结果表明，衔接分子CARMA1和Bcl10对这一过程至关重要。此外，已确定MALT1/类旁胱天蛋白酶起着关键作用。MALT1、CARMA1和Bcl10形成一个三方蛋白复合物，其中Bcl10被认为有助于MALT1单体的寡聚化。如在一部分淋巴瘤患者中观察到的那样，MALT1的过表达会导致NF-κB的强力激活，这表明MALT1可能（直接或间接）刺激负责激活细胞质NF-κB以便转运到细胞核中的激酶复合物[IKK，NF-κB（IkappaB）激酶抑制剂]。此外，MALT1-CARMA1-Bcl10复合物负责NEMO的泛素化，这一步骤似乎对TCR诱导的NF-κB激活至关重要，但对由其他刺激（如TNF或IL-1）介导的诱导并不重要。
