IDENTIFICATION OF AN INVASION-INDUCING GENE, TIAM-1, THAT ENCODES A PROTEIN WITH HOMOLOGY TO GDP-GTP EXCHANGERS FOR RHO-LIKE PROTEINS
IDENTIFICATION OF AN INVASION-INDUCING GENE, TIAM-1, THAT ENCODES A PROTEIN WITH HOMOLOGY TO GDP-GTP EXCHANGERS FOR RHO-LIKE PROTEINS
复制标题
DOI：
10.1016/0092-8674(94)90216-x
复制
发表时间：
1994-05-20
期刊：
影响因子：
64.5
通讯作者：
COLLARD, JG
中科院分区：
文献类型：
--
作者：
HABETS, GGM;SCHOLTES, EHM;COLLARD, JG
使用前病毒标签与体外侵袭性选择相结合，我们已经鉴定出一个影响侵袭的基因，命名为Tiam-1。在选定的侵袭性T淋巴瘤变体中，在Tiam-1基因的编码外显子内发现前病毒插入，导致截短的5 '端和3'端转录物，产生N-和C-末端Tiam-1蛋白片段。在一种侵袭性变异中，观察到Tiam-1基因座的扩增伴随着正常Tiam-1蛋白量的增加。体外侵袭性的细胞克隆在裸鼠中产生实验性转移，将截短的Tiam-1 cDNA转染到非侵袭性细胞中使这些细胞具有侵袭性。预测的Tiam-1蛋白含有一个Dbl和Pleckstrin同源结构域，它与GDP-GTP交换器共享Rho样蛋白，这些蛋白与细胞骨架组织有关。
Using proviral tagging in combination with in vitro selection for invasiveness, we have identified a gene, designated Tiam-1, that affects invasion. In the selected invasive T lymphoma variants, proviral insertions were found within coding exons of the Tiam-1 gene, resulting in both truncated 5'-end and 3'-end transcripts that give rise to N- and C-terminal Tiam-1 protein fragments. In one invasive variant, amplification of the Tiam-1 locus was observed with concomitant increase in the amount of normal Tiam-1 protein. Cell clones that were invasive in vitro produced experimental metastases in nude mice, and transfection of truncated Tiam-1 cDNAs into noninvasive cells made these cells invasive. The predicted Tiam-1 protein harbors a Dbl- and Pleckstrin-homologous domain, which it shares with GDP-GTP exchangers for Rho-like proteins that have been implicated in cytoskeletal organization.