Azim A C, Knoll J H, Marfatia S M, Peel D J, Bryant P J, Chishti A H
Department of Biomedical Research, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Genomics. 1995 Dec 10;30(3):613-6. doi: 10.1006/geno.1995.1286.
The Drosophila discs large tumor suppressor protein, Dlg, is the prototype of a newly discovered family of proteins termed MAGUKs (membrane-associated guanylate kinase homologues). MAGUKs are localized at the membrane-cytoskeleton interface, usually at cell-cell junctions, where they appear to have both structural and signaling roles. They contain several distinct domains, including a modified guanylate kinase domain, an SH3 motif, and one or three copies of the DHR (GLGF/PDZ) domain. Recessive lethal mutations in the discs large tumor suppressor gene interfere with the formation of septate junctions (thought to be the arthropod equivalent of tight junctions) between epithelial cells, and they cause neoplastic overgrowth of imaginal discs, suggesting a role for cell junctions in proliferation control. A homologue of the Dlg protein, named Hdlg, has been isolated from human B lymphocytes. It shows 65-79% identity to Dlg in the different domains, and it binds to the cytoskeletal protein 4.1. Here, we report that the gene for lymphocyte Hdlg, named DLG1, is located at chromosome band 3q29. This finding identifies a novel site for a candidate tumor suppressor on chromosome 3.
果蝇盘大肿瘤抑制蛋白Dlg是新发现的一类称为MAGUKs（膜相关鸟苷酸激酶同源物）的蛋白质的原型。MAGUKs定位于膜 - 细胞骨架界面，通常在细胞间连接处，在那里它们似乎兼具结构和信号传导作用。它们包含几个不同的结构域，包括一个修饰的鸟苷酸激酶结构域、一个SH3基序以及一个或三个DHR（GLGF/PDZ）结构域拷贝。盘大肿瘤抑制基因中的隐性致死突变会干扰上皮细胞之间分隔连接（被认为是节肢动物中紧密连接的等效物）的形成，并且会导致成虫盘的肿瘤性过度生长，这表明细胞连接在增殖控制中起作用。已从人B淋巴细胞中分离出Dlg蛋白的一个同源物，名为Hdlg。它在不同结构域中与Dlg有65 - 79%的同一性，并且它与细胞骨架蛋白4.1结合。在此，我们报告淋巴细胞Hdlg的基因，命名为DLG1，位于染色体带3q29。这一发现确定了3号染色体上一个候选肿瘤抑制基因的新位点。
