Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.

Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.
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DOI:
10.1016/j.semcancer.2009.03.002
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发表时间:
2009-08
影响因子:
14.5
通讯作者:
Schaffhausen BS
Schaffhausen BS
中科院分区:
医学1区
文献类型:
--
作者:
Cheng J;DeCaprio JA;Fluck MM;Schaffhausen BS

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猿猴病毒40 (SV40)和小鼠多瘤病毒(PY)是小的DNA肿瘤病毒,已广泛用于研究细胞转化。SV40早期区编码三种肿瘤抗原,大T (LT),小T (ST)和17KT,有助于细胞转化。虽然PY也编码LT和ST,但唯一的中间T (MT)产生了大部分的转化活动。SV40 LT介导的转化需要结合细胞核中的肿瘤抑制蛋白Rb和p53, ST结合细胞质中的蛋白磷酸酶PP2A。SV40 LT还结合其他几种促进病毒转化的细胞蛋白,包括p300、CBP、Cul7、IRS1、Bub1、Nbs1和Fbw7。PY MT转化依赖于PP2A和Src家族蛋白酪氨酸激酶(PTK)的结合,以及细胞膜上信号复合物的组装,从而以类似于Her2/neu的方式导致转化。MT酪氨酸残基的磷酸化激活了包括Shc/Grb2、PI3K和plc - γ1在内的关键信号分子。SV40 LT、ST和PY MT对细胞转化的独特贡献为我们理解肿瘤抑制因子、癌基因和肿瘤发生过程提供了重要的见解。
Simian Virus 40 (SV40) and Mouse Polyoma Virus (PY) are small DNA tumor viruses that have been used extensively to study cellular transformation. The SV40 early region encodes three tumor antigens, Large T (LT), small T (ST) and 17KT that contribute to cellular transformation. While PY also encodes LT and ST, the unique Middle T (MT) generates most of the transforming activity. SV40 LT mediated transformation requires binding to the tumor suppressor proteins Rb and p53 in the nucleus and ST binding to the protein phosphatase PP2A in the cytoplasm. SV40 LT also binds to several additional cellular proteins including p300, CBP, Cul7, IRS1, Bub1, Nbs1 and Fbw7 that contribute to viral transformation. PY MT transformation is dependent binding to PP2A and the Src family protein tyrosine kinases (PTK) and assembly of a signaling complex on cell membranes that leads to transformation in a manner similar to Her2/neu. Phosphorylation of MT tyrosine residues activates key signaling molecules including Shc/Grb2, PI3K and PLCγ1. The unique contributions of SV40 LT and ST and PY MT to cellular transformation have provided significant insights into our understanding of tumor suppressors, oncogenes and the process of oncogenesis.
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