A tumor host range selection procedure identifies p150sal2 as a target of polyoma virus large T antigen

A tumor host range selection procedure identifies p150sal2 as a target of polyoma virus large T antigen
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DOI:
10.1073/pnas.251447198
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发表时间:
2001-12-04
影响因子:
11.1
通讯作者:
Benjamin, TL
Benjamin, TL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li, DW;Dower, K;Benjamin, TL

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癌细胞可能会经历某些病毒通常靶向促进病毒复制的功能的丧失或改变。失去靶向功能的病毒突变体应该能够在这样的癌细胞中生长,但不能在正常细胞中生长。基于这一原理,设计了一种“肿瘤宿主范围”(t-hr)选择程序并应用于多瘤病毒。对一个t-hr突变体的研究已经鉴定出mSal 2基因产物(p150(sal 2))作为大T抗原的结合伴侣。mSal 2编码一个多锌指蛋白和假定的转录因子,与果蝇同源异型基因Spalt同源。t-hr突变体编码一种改变的大T蛋白,该蛋白不能与p150(sal 2)相互作用,并且在新生小鼠中的复制和肿瘤诱导中存在缺陷。
Cancer cells may undergo loss or alterations in functions that certain viruses normally target to promote virus replication. Virus mutants that have lost the targeting function(s) should be able to grow in such cancer cells but not in normal cells. A "tumor host range" (t-hr) selection procedure has been devised and applied to polyoma virus based on this rationale. Studies of one t-hr mutant have led to the identification of the mSal2 gene product (p150(sal2)) as a binding partner of the large T antigen. mSal2 encodes a multizinc finger protein and putative transcription factor homologous to the Drosophila homeotic gene Spalt. The t-hr mutant encodes an altered large T protein that fails to interact with p150(sal2) and is defective in replication and tumor induction in newborn mice.