The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton.
The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton.
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果蝇致命（2）巨型幼虫抑制蛋白是细胞骨架的组成部分。
DOI：
10.1083/jcb.127.5.1345
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发表时间：
1994-12
期刊：
影响因子：
--
通讯作者：
Mechler BM
中科院分区：
文献类型：
--
作者：
Strand D;Raska I;Mechler BM
肿瘤抑制基因作为癌症的隐性决定因素。在果蝇中，这些基因在正常发育中发挥作用，并且对于调节细胞生长和分化至关重要。致死性巨幼虫l（2）gl基因的突变，除了在大脑和成虫盘中引起恶性肿瘤外，还在许多其他组织中产生发育缺陷。关于l（2）gl基因产物p127的功能的许多不确定性是由于缺乏关于该蛋白在细胞中的精确位置的知识。我们已经调查了细胞和亚细胞定位的p127，使用共聚焦和电子显微镜以及生化和细胞分级程序。我们的分析表明，p127是完全位于细胞内的细胞质和绑定到细胞连接区域的侧细胞膜的内面。在膜上，p127可以形成大的聚集体，其抵抗非离子去污剂的溶解，表明p127参与细胞骨架基质。这些发现表明，在肿瘤组织中观察到的细胞形状的变化和顶端-基底极性的丧失是由l（2）gl失活引起的细胞骨架组织改变的直接结果，也表明p127参与了以细胞间隙为基础的细胞间通讯系统，指导细胞分化。
Tumor suppressor genes act as recessive determinants of cancer. In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imaginal discs, generate developmental defects in a number of other tissues. Much of the uncertainty regarding the function of the l(2)gl gene product, p127, results from a lack of knowledge as to the precise location of this protein in the cell. We have investigated the cellular and subcellular localization of p127, using confocal and electron microscopy as well as biochemical and cell fractionation procedures. Our analyses indicate that p127 is located entirely within the cell in both the cytoplasm and bound to the inner face of lateral cell membranes in regions of cell junctions. On the membrane, p127 can form large aggregates which are resistant to solubilization by nonionic detergents, indicating that p127 is participating in a cytoskeletal matrix. These findings suggest that the changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organization caused by l(2)gl inactivation and also suggest that p127 is involved in a cytoskeletal-based intercellular communication system directing cell differentiation.