Deletion of proline-rich domain in polyomavirus T antigens results in virus partially defective in transformation and tumorigenesis.
Deletion of proline-rich domain in polyomavirus T antigens results in virus partially defective in transformation and tumorigenesis.
复制标题
多瘤病毒T抗原中富含脯氨酸的结构域的缺失会导致病毒在转化和肿瘤发生方面存在部分缺陷。
DOI：
10.1006/viro.1998.9246
复制
发表时间：
1998
期刊：
影响因子：
3.7
通讯作者：
Freund,R
中科院分区：
文献类型：
--
作者：
Yi,X;Freund,R
多瘤病毒有效感染小鼠细胞，在培养中转化大鼠成纤维细胞，并且当接种到新生小鼠中时诱导广谱肿瘤。大、中、小T抗原的表达是病毒生长和致癌转化所必需的。我们已经在编码三个连续脯氨酸的大T抗原和中T抗原共同的区域中产生了一个小的缺失。在这份报告中，我们描述了这种突变病毒在小鼠细胞中复制，转化大鼠成纤维细胞和诱导小鼠肿瘤的能力。我们发现，病毒永生原代细胞和病毒DNA复制不受损害，表明这些功能的大T抗原没有改变。然而，病毒转化大鼠成纤维细胞的能力是有缺陷的。突变病毒产生的病灶较少，病灶外观较弱。突变的中间T仍然与PI 3-激酶和shc相关联，这表明蛋白质的整体结构没有被破坏。当接种到新生C3 H小鼠中时，突变病毒比野生型病毒诱导的总体肿瘤更少，潜伏期更长。这些结果表明，中T抗原中的这个富含脯氨酸的结构域对于多种组织和细胞类型的肿瘤发生非常重要。
Polyomavirus productively infects mouse cells, transforms rat fibroblasts in culture, and induces a broad spectrum of tumors when inoculated into newborn mice. The expression of large, middle, and small T antigen are necessary for virus growth and oncogenic transformation. We have generated a small deletion in a region common to both large and middle T antigen that encodes three consecutive prolines. In this report we characterize this mutant virus in terms of its ability to replicate in mouse cells, transform rat fibroblasts, and induce tumors in the mouse. We find that the virus immortalizes primary cells and that viral DNA replication is not impaired, indicating that these functions of large T antigen are not altered. However, the ability of the virus to transform rat fibroblasts is defective. The mutant virus makes fewer foci and the foci are weaker in appearance. The mutant middle T still associates with PI 3-kinase and shc, suggesting that the overall structure of the protein has not been disrupted. When inoculated into newborn C3H mice, the mutant virus induces fewer overall tumors with a longer latency than wild-type virus. These results indicate that this proline-rich domain in middle T antigen is important for oncogenesis in a wide variety of tissues and cell types.