Identification of specific PP2A complexes involved in human cell transformation

Identification of specific PP2A complexes involved in human cell transformation
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DOI:
10.1016/s1535-6108(04)00026-1
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发表时间:
2004-02-01
期刊:
影响因子:
50.3
通讯作者:
Hahn, WC
Hahn, WC
中科院分区:
医学1区
文献类型:
--
作者:
Chen, W;Possemato, R;Hahn, WC

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SV 40小t抗原(ST)与丝氨酸-苏氨酸蛋白磷酸酶2A(PP 2A)相互作用。为了研究这种相互作用在转化中的作用,我们抑制了表达SV 40大T抗原、hTERT和H-RAS的人胚肾(HEK)上皮细胞中PP 2A B56 γ亚基的表达。PP 2A B56 γ表达的抑制抑制PP 2A特异性磷酸酶活性,类似于ST所实现的,并赋予以锚定非依赖性方式生长和形成肿瘤的能力。PP 2A B56 γ 3在表达ST的致瘤HEK细胞或人肺癌细胞系中的过表达部分逆转了这些细胞的致瘤性。这些观察鉴定了参与人细胞转化的特定PP 2A复合物。
The SV40 small t antigen (ST) interacts with the serine-threonine protein phosphatase 2A (PP2A). To investigate the role of this interaction in transformation, we suppressed the expression of the PP2A B56gamma subunit in human embryonic kidney (HEK) epithelial cells expressing SV40 large T antigen, hTERT, and H-RAS. Suppression of PP2A B56gamma expression inhibited PP2A-specific phosphatase activity similar to that achieved by ST and conferred the ability to grow in an anchorage-independent fashion and to form tumors. Overexpression of PP2A B56gamma3 in tumorigenic HEK cells expressing ST or human lung cancer cell lines partially reversed the tumorigenicity of these cells. These observations identify specific PP2A complexes involved in human cell transformation.