Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival.
Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival.
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DOI：
10.2174/138920310791824011
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发表时间：
2010-09
影响因子：
2.8
通讯作者：
Yu Q
中科院分区：
文献类型：
--
作者：
Stamenkovic I;Yu Q
神经纤维瘤病2型（NF 2）基因的遗传改变导致神经鞘瘤、脑膜瘤和室管膜瘤的发生。在甲状腺癌、间皮瘤和黑色素瘤中也发现了NF 2基因的突变，这表明它在广泛的细胞中起着肿瘤抑制剂的作用。NF 2基因的产物为merlin（moesinezrin-radixin-like protein），属于Band 4.1超家族蛋白。Merlin与ERM（Ezrin-Radixin-Moesin）家族蛋白具有显著的序列同源性，并作为跨膜蛋白和肌动蛋白-细胞骨架之间的接头。Merlin是一种多功能蛋白，参与整合和调节细胞外信号和细胞内信号通路，控制细胞命运、形状、增殖、存活和运动。最近的研究表明，merlin调节细胞-细胞和细胞-基质粘附以及包括CD 44在内的细胞表面粘附/细胞外基质受体的功能，并且merlin和CD 44拮抗彼此的功能并在哺乳动物Hippo信号传导途径的上游起作用。此外，merlin在稳定增殖的接触抑制和调节几种受体酪氨酸激酶的活性中起重要作用。积累的数据也表明，梅林作为几种非NF 2相关癌症类型的生长和进展的负调节剂的作用正在显现。总之，这些最新的进展提高了我们对梅林功能，其调节，以及梅林调节的主要信号通路的基本理解，并为将来将这些发现转化为临床为患有梅林功能和/或其下游信号通路受损或改变的癌症患者提供了基础。
Genetic alterations of neurofibromatosis type 2 (NF2) gene lead to the development of schwannomas, meningiomas, and ependymomas. Mutations of NF2 gene were also found in thyroid cancer, mesothelioma, and melanoma, suggesting that it functions as a tumor suppressor in a wide spectrum of cells. The product of NF2 gene is merlin (moesinezrin-radixin-like protein), a member of the Band 4.1 superfamily proteins. Merlin shares significant sequence homology with the ERM (Ezrin-Radixin-Moesin) family proteins and serves as a linker between transmembrane proteins and the actin-cytoskeleton. Merlin is a multifunctional protein and involved in integrating and regulating the extracellular cues and intracellular signaling pathways that control cell fate, shape, proliferation, survival, and motility. Recent studies showed that merlin regulates the cell-cell and cell-matrix adhesions and functions of the cell surface adhesion/extracellular matrix receptors including CD44 and that merlin and CD44 antagonize each other's function and work upstream of the mammalian Hippo signaling pathway. Furthermore, merlin plays important roles in stabilizing the contact inhibition of proliferation and in regulating activities of several receptor tyrosine kinases. Accumulating data also suggested an emerging role of merlin as a negative regulator of growth and progression of several non-NF2 associated cancer types. Together, these recent advances have improved our basic understanding about merlin function, its regulation, and the major signaling pathways regulated by merlin and provided the foundation for future translation of these findings into the clinic for patients bearing the cancers in which merlin function and/or its downstream signaling pathways are impaired or altered.
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影响因子：
4.8
作者：
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通讯作者：
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