Regulation of cytoskeletal association by a basic amino acid motif in polyoma virus middle T antigen

被引:9
作者
Elliott, J [1 ]
Jones, MD [1 ]
Griffin, BE [1 ]
Krauzewicz, N [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Infect Dis, London W12 0NN, England
基金
英国医学研究理事会;
关键词
CaaX box; cytoskeleton; green fluorescent protein; middle T antigen;
D O I
10.1038/sj.onc.1202083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The subcellular localization of many oncogenic proteins is thought to be important for their function. In the case of the middle T antigen of the DNA tumour virus, polyoma, localization to membranes in a specific manner is essential for its cellular transforming activity. To investigate factors that influence this localization, heterologous membrane targetting sequences were substituted for the middle T antigen transmembrane domain and the properties of the resulting proteins studied. Whereas G-terminal lipid modification derived from the H-ras CaaX box restored oncogenic activity to nontransforming truncated middle T antigen species, N-terminal myristylation from pp60c-src did not. Furthermore, a region, rich in basic amino acids and adjacent to the middle T transmembrane domain, was found to mediate association with detergent-insoluble cytoskeleton. Go-operation between the basic motif and neighbouring membrane binding domains resulted in specific localization of proteins to particular membrane sites, characterized by the association with subcellular structures, likely to be cytoskeletal in nature. These results demonstrate that the cellular localization of MT is regulated by at least two determinants, a transmembrane sequence which confers membrane binding and a basic motif which specifies a particular site within the membrane.
引用
收藏
页码:1797 / 1806
页数:10
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