Okada Tomoyo, You Liru, Giancotti Filippo G
Cell Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Trends Cell Biol. 2007 May;17(5):222-9. doi: 10.1016/j.tcb.2007.03.006. Epub 2007 Apr 17.
Inactivation of the tumor suppressor Merlin, encoded by the NF2 (Neurofibromatosis type 2) gene, contributes to malignant conversion in many cell types. Merlin is an Ezrin-Radixin-Moesin protein and localizes underneath the plasma membrane at cell-cell junctions and other actin-rich sites. Recent studies indicate that Merlin mediates contact inhibition of proliferation by blocking recruitment of Rac to the plasma membrane. In mitogen-stimulated cells, p21-activated kinase phosphorylates Ser518 in the C-terminus of Merlin, inactivating the growth suppressive function of the protein. Furthermore, the myosin phosphatase MYPT1-PP1delta, has been identified as a direct activator of Merlin and its inhibition has been linked to malignant transformation. Finally, studies in the fruit fly Drosophila melanogaster have revealed that Merlin functions together with the band 4.1 protein Expanded to promote [corrected] the endocytosis of many signaling receptors, limiting [corrected] their accumulation at the plasma membrane, and to activate [corrected] the Hippo signaling pathway. Here, we review these recent findings and their relevance to the tumor suppressor function of Merlin.
由NF2（神经纤维瘤病2型）基因编码的肿瘤抑制因子Merlin的失活，在许多细胞类型中促成恶性转化。Merlin是一种埃兹蛋白-根蛋白-膜突蛋白，定位于细胞间连接和其他富含肌动蛋白的位点的质膜下方。最近的研究表明，Merlin通过阻止Rac募集到质膜来介导增殖的接触抑制。在有丝分裂原刺激的细胞中，p21活化激酶使Merlin C末端的Ser518磷酸化，从而使该蛋白的生长抑制功能失活。此外，肌球蛋白磷酸酶MYPT1-PP1δ已被鉴定为Merlin的直接激活剂，其抑制作用与恶性转化有关。最后，对果蝇的研究表明，Merlin与4.1带蛋白Expanded共同发挥作用，促进许多信号受体的内吞作用，限制它们在质膜上的积累，并激活Hippo信号通路。在此，我们综述这些最新发现及其与Merlin肿瘤抑制功能的相关性。
