Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in transformation.
Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in transformation.
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转化中的Jaagsiekte绵羊逆转录病毒（JSRV）包膜蛋白结构域的分析。
DOI：
10.1007/s11262-012-0793-y
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发表时间：
2012-12
期刊：
影响因子：
1.6
通讯作者：
Fan, Hung
中科院分区：
文献类型：
--
作者：
Hull, Stacey;Lim, Joohyun;Hamil, Alexander;Nitta, Takayuki;Fan, Hung
绵羊肺腺病毒（Jaagsiekte sheep retrovirus，JSRV）是绵羊传染性肺癌的病原体。一个独特的特征是JSRV包膜蛋白也是该病毒的致癌基因。以前的研究已经确定了包膜跨膜（TM）蛋白质的胞质尾作为关键的转化，虽然其他地区的Env也有牵连。在这项研究中，其他Env区域在转化中的作用进行了研究。使用JSRV Env和相关的非致癌内源性逆转录病毒（enJSRV，56 A1）的Env之间的嵌合体。含有插入到JSRV Env中的enJSRV的跨膜区（MSR）的嵌合体显示显著减少的转化，表明MSR在转化中起作用。该嵌合体的转化高度依赖于Ras/Raf/MEK/MAPK和PI 3 K/Akt/mTOR信号传导。在TM胞外域中含有区分JSRV和enJSRV的两个氨基酸的嵌合体显示出适度减少的转化。SU蛋白中的嵌合体表明SU的氨基末端区域有助于转化，而C-末端部分不重要。为了测试Env三聚化对于转化是否重要，我们突变了TM（Tri-M）胞外域中推定的三聚化结构域中的富含亮氨酸的序列。该突变体不能转化细胞，也不能寡聚化。然而，Tri-M可以补充非转化突变体胞质尾突变体（Y 590 F），因此寡聚化对于转化的至少一些方面不是必需的。这些实验提供了新的见解的区域和残基的JSRV Env蛋白致癌转化所必需的。
Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a transmissible lung cancer in sheep. A unique feature is that JSRV envelope protein is also the oncogene for this virus. Previous studies have identified the cytoplasmic tail of the envelope transmembrane (TM) protein as critical for transformation, although other regions of Env have also been implicated. In this study, the roles of other Env regions in transformation were investigated. Chimeras between JSRV Env and the Env of a related non-oncogenic endogenous retrovirus (enJSRV, 56A1) were used. A chimera containing the membrane-spanning region (MSR) of enJSRV inserted into JSRV Env showed substantially reduced transformation, indicating that the MSR plays a role in transformation. Transformation by this chimera was highly dependent on both Ras/Raf/MEK/MAPK and PI3K/Akt/mTOR signaling. A chimera containing the two amino acids in the TM ectodomain that distinguish JSRV and enJSRV showed modestly reduced transformation. Chimeras in the SU protein indicated that the amino terminal region of SU contributes to transformation, while the C-terminal part is not important. To test if Env trimerization is important for transformation, we mutated a leucine-rich sequence in the putative trimerization domain in the ectodomain of TM (Tri-M). This mutant could not transform cells, and it did not oligomerize. However Tri-M could complement a non-transforming mutant cytoplasmic tail mutant (Y590F), so oligomerization is not necessary for at least some aspects of transformation. These experiments provide new insight into the regions and residues of JSRV Env protein necessary for oncogenic transformation.
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DOI：
10.1073/pnas.0837136100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Danilkovitch-Miagkova, A;Duh, FM;Lerman, MI
通讯作者：
Lerman, MI
影响因子：
64.8
作者：
Liu, Jun;Bartesaghi, Alberto;Borgnia, Mario J.;Sapiro, Guillermo;Subramaniam, Sriram
通讯作者：
Subramaniam, Sriram
影响因子：
5.4
作者：
Hofacre, A;Fan, H
通讯作者：
Fan, H
影响因子：
5.4
作者：
Dirks, C;Duh, FM;Miller, AD
通讯作者：
Miller, AD
影响因子：
5.4
作者：
Liu, SL;Lerman, MI;Miller, AD
通讯作者：
Miller, AD