MALT1 protease: a new therapeutic target in B lymphoma and beyond?
MALT1 protease: a new therapeutic target in B lymphoma and beyond?
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DOI：
10.1158/1078-0432.ccr-11-0467
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发表时间：
2011-11-01
期刊：
影响因子：
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通讯作者：
Lucas PC
中科院分区：
文献类型：
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作者：
McAllister-Lucas LM;Baens M;Lucas PC
MALT 1作为B细胞肿瘤MALT淋巴瘤中受干扰的基因的鉴定已经是十多年前的事了，这是一个密集研究领域的起点。对MALT 1的迷恋进一步被观察到，它包含一个与半胱天冬酶催化结构域同源的结构域，因此可能作为蛋白酶发挥作用。此后的发现最初揭示了MALT 1是抗原受体信号传导至转录因子NF-κB的关键衔接分子，NF-κB对淋巴细胞功能至关重要。然而，最近的发现表明，MALT 1的这种功能并不局限于淋巴细胞，这可以从越来越多的来自免疫系统内外的细胞的受体列表中得到证明，这些细胞需要MALT 1来激活NF-κB。然而，MALT 1蛋白酶活性仅在最近才在免疫信号传导中被证实，并且其重要性随后通过NF-κ B成瘾的B细胞淋巴瘤对这种蛋白水解活性的依赖性而进一步加强。因此，MALT 1蛋白酶活性的治疗靶向可能成为治疗这些淋巴瘤的有用方法，此外，也是治疗与NF-κB信号失调相关的其他肿瘤性和炎症性疾病的有效策略。
The identification of MALT1 as a gene that is perturbed in the B cell neoplasm MALT lymphoma, already more than a decade ago, was the starting point for an intense area of research. The fascination with MALT1 was fueled further by the observation that it contains a domain homologous to the catalytic domain of caspases and thus potentially could function as a protease. Discoveries since then initially revealed that MALT1 is a key adaptor molecule in antigen receptor signaling to the transcription factor NF-κB, which is crucial for lymphocyte function. However, recent discoveries show that this function of MALT1 is not restricted to lymphocytes, witnessed by the ever increasing list of receptors from cells within and outside of the immune system that require MALT1 for NF-κB activation. Yet, a role for MALT1 protease activity was demonstrated only recently in immune signaling and its importance was then further strengthened by the dependency of NF-κB-addicted B cell lymphomas on this proteolytic activity. Therapeutic targeting of MALT1 protease activity might therefore become a useful approach for the treatment of these lymphomas, and additionally, an effective strategy for treating other neoplastic and inflammatory disorders associated with deregulated NF-κB signaling.