Characterization of a tumor-associated gene, a member of a novel family of genes encoding membrane glycoproteins
Characterization of a tumor-associated gene, a member of a novel family of genes encoding membrane glycoproteins
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DOI：
10.1016/s0378-1119(96)00475-1
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发表时间：
1996-12-12
期刊：
影响因子：
3.5
通讯作者：
Benvenisty, N
中科院分区：
文献类型：
--
作者：
BenPorath, I;Benvenisty, N
为了分离参与肿瘤形成和胚胎发生的基因，从 c-myc 诱导的小鼠脑肿瘤构建了消减 cDNA 文库。在此筛选中分离出的基因名为 TMP（肿瘤相关膜蛋白），编码具有四个跨膜结构域的推定糖蛋白。研究发现TMP基因在脑肿瘤细胞中高表达，但在正常脑中不表达。它也在未分化的胚胎干细胞中高水平表达，但在这些细胞分化成胚状体后显着下调。 TMP 氨基酸序列与生长停滞特异性蛋白 PMP22/GAS-3 具有高度同源性，该蛋白与多种人类周围神经病有关。比较不同增殖状态下NIH-3T3成纤维细胞中TMP和PMP22基因的表达模式。结果表明两种同源物的表达模式相反，TMP 在细胞增殖期间表达较高，PMP22 在生长停滞期间表达较高。为了进一步表征 TMP 基因，我们分离了其人类同源物并检查了其在胚胎和成人组织中的表达。在寻找与 TMP 和 PMP22 同源的人类序列时，我们鉴定了两个新基因，将其命名为 XMP 和 YMP。因此，我们提出了一个新的膜糖蛋白家族，其中一个成员与增殖密切相关，另一个成员与生长停滞密切相关。
To isolate genes involved in tumor formation and in embryogenesis, a subtracted cDNA library was constructed from a c-myc-induced mouse brain tumor. A gene isolated in this screen, named TMP (tumor-associated membrane protein), codes for a putative glycoprotein with four transmembrane domains. The TMP gene was found to be highly expressed in brain tumor cells but not in normal brain. It is also expressed at high levels in undifferentiated embryonic stem cells, but markedly down-regulated in these cells after their differentiation into embryoid bodies. The TMP amino acid sequence bears high homology to the growth arrest specific protein PMP22/GAS-3, which is involved in several human peripheral neuropathies. The expression patterns of the TMP and PMP22 genes in NIH-3T3 fibroblasts were compared at different proliferation states. The results suggest an inverse pattern of expression for the two homologs, TMP expression being high during cell proliferation and PMP22 expression being high during growth arrest. To further characterize the TMP gene we have isolated its human homolog and examined its expression in embryonic and adult tissues. In our search for human sequences homologous to TMP and PMP22, we identified two new genes which we have named XMP and YMP. Thus, we present a novel family of membrane glycoproteins, one member of which is closely associated with proliferation and another with growth arrest.