Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein:: enhancement of transformation and transactivation
Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein:: enhancement of transformation and transactivation
复制标题
DOI：
10.1038/sj.onc.1202967
复制
发表时间：
1999-10-07
期刊：
影响因子：
8
通讯作者：
Lüscher, B
中科院分区：
文献类型：
--
作者：
Lüscher-Firzlaff, JM;Westendorf, JM;Lüscher, B
高风险人乳头瘤病毒 (HPV) 16 型 E7 蛋白通过干扰细胞蛋白的功能来影响细胞生长控制并促进转化。 E7 的一个 keg 靶点是肿瘤抑制蛋白 p105RB。虽然这种相互作用是 E7 依赖性转化所必需的，但其他细胞分子也必须参与其中，因为一些转化能力降低的 E7 突变体仍然与 p10RB 结合。为了鉴定与 E7 相互作用并可能负责介导其转化功能的其他蛋白质，我们在酵母双杂交筛选中使用了 E7 的 C 端一半。我们将叉头结构域转录因子喜相磷蛋白 2 (MPP2) 鉴定为 E7 的相互作用伴侣，在哺乳动物细胞中检测到 tno 蛋白在比例和体内的特异性相互作用。 MPP2 与 E7 的相互作用在功能上是相关的，因为 MPP2 增强了大鼠胚胎成纤维细胞的 E7/Ha-Ras 共转化。此外，HPV16 E7，但HPV16 E7的非转化突变体和低风险HPV6 E7都不能刺激MPP2特异性转录活性。因此，MPP2 是 E7 介导的转化的潜在重要靶标。
The high risk human papillomavirus (HPV) type 16 E7 protein affects cell growth control and promotes transformation by interfering with functions of cellular proteins. A keg target of E7 is the tumor suppressor protein p105RB. Although this interaction is required for E7-dependent transformation, other cellular molecules must also be involved, because some E7 mutants that have reduced transforming abilities still bind to p10RB. In order to identify additional proteins that interact with E7 and that may be responsible to mediate its transforming function, we have used the C-terminal half of E7 in a yeast two-hybrid screen. We identified the fork head domain transcription factor hi phase phosphoprotein 2 (MPP2) as an interaction partner of E7, Specific interaction of the tno proteins both in ratio and in vivo in mammalian cells was detected. The interaction of MPP2 with E7 is functionally relevant since MPP2 enhances the E7/Ha-Ras co-transformation of rat embryo fibroblasts. In addition HPV16 E7, but neither non-transforming mutants of HPV16 E7 nor low risk HPV6 E7, was able to stimulate MPP2-specific transcriptional activity. Thus, MPP2 is a potentially important target for E7-mediated transformation.