Biogem Consortium, Ariano, Italy.
J Cell Physiol. 2014 Aug;229(8):990-7. doi: 10.1002/jcp.24543.
Initially identified by their ability to modulate the functional activity of BCL10, the three CARMA proteins, CARMA1, -2, and -3, have recently themselves taken a leading role on the stage of molecular medicine. Although considered for some time as simple ancillary proteins, increasingly accumulating recent data evidently indicate a role of primary importance for these three proteins in the pathophysiology of several human tumors and inflammatory disorders. In fact, recent scientific literature clearly establishes that CARMA1 is one of the most mutated genes in a subtype of B-cell lymphoma and, at the same time, responsible for some rare human immunodeficiency conditions. On the other hand, mutations in CARMA2 are responsible for the hereditary transmission of some inflammatory disorders of the skin, including familial psoriasis and ptiriasis; whereas expression of CARMA3 appears to be deregulated in different human tumors. Here we describe and summarize the mutations found in the genes coding for the three CARMA proteins in these different human pathological conditions, and offer an interpretation of the molecular mechanisms from which arise the biological outcomes in which these proteins are involved.
最初因其能够调节 BCL10 的功能活性而被识别，CARMA 蛋白家族的三个成员 CARMA1、-2 和 -3，最近在分子医学的舞台上扮演了重要角色。尽管这些蛋白在一段时间内被认为是简单的辅助蛋白，但越来越多的最新数据显然表明，这三种蛋白在几种人类肿瘤和炎症性疾病的病理生理学中具有重要作用。事实上，最近的科学文献清楚地表明，CARMA1 是 B 细胞淋巴瘤的一种亚型中突变最多的基因之一，同时也是一些罕见人类免疫缺陷疾病的罪魁祸首。另一方面，CARMA2 的突变导致包括家族性银屑病和 ptiriasis 在内的一些皮肤炎症性疾病的遗传性传播；而 CARMA3 的表达似乎在不同的人类肿瘤中失调。在这里，我们描述并总结了编码这三种 CARMA 蛋白的基因在这些不同人类病理条件下的突变，并对这些蛋白所涉及的分子机制及其产生的生物学结果进行了解释。
