Identification of PP2A complexes and pathways involved in cell transformation.
Identification of PP2A complexes and pathways involved in cell transformation.
复制标题
鉴定PP2A复合物和参与细胞转化的途径。
DOI：
10.1158/0008-5472.can-10-2855
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发表时间：
2010-12-15
期刊：
影响因子：
11.2
通讯作者：
Hahn WC
中科院分区：
文献类型：
--
作者：
Sablina AA;Hector M;Colpaert N;Hahn WC
猴病毒40小t(SV40ST)癌蛋白与蛋白磷酸酶2A(PP2A)相互作用，PP2A是一个丰富表达的丝氨酸-苏氨酸磷酸酶家族。这种相互作用是SV40转化人类细胞所必需的，几个PP2A亚单位被认为是肿瘤抑制基因。然而，由参与细胞转化的特定PP2A复合体控制的通路仍然不完全清楚。采用综合功能丧失的方法，我们确定了四个PP2A调节亚基(B56α，B56γ，Pr72/Pr130和PTPA)，当被抑制时，它们在人类细胞转化中取代了SV40ST的表达。我们发现，含有PP2A B56α、B56γ和Pr72/PR130的复合体的操作激活了c-Myc、Wnt和PI3K/Akt调控的通路，这种激活方式取决于它们的特定磷酸酶活性。相反，抑制PTPA会扰乱PP2A异三聚体复合体的组装，从而导致这些相同的致癌途径的激活。这些观察描绘了在人类细胞转化过程中受SV40ST干扰的PP2A家族成员和途径。
The simian virus 40 small t (SV40ST) oncoprotein interacts with protein phosphatase 2A (PP2A), an abundantly expressed family of serine-threonine phosphatases. This interaction is essential for the transformation of human cells by SV40, and several PP2A subunits have been implicated as tumor suppressor genes. However, the pathways controlled by specific PP2A complexes involved in cell transformation remain incompletely understood. Using a comprehensive loss-of-function approach, we identified four PP2A regulatory subunits (B56α, B56γ, PR72/PR130 and PTPA) that when suppressed replaced the expression of SV40ST in human cell transformation. We found that manipulation of complexes containing PP2A B56α, B56γ and PR72/PR130 activates the pathways regulated by c-Myc, Wnt, and PI3K/Akt in a manner that depends on their specific phosphatase activity. In contrast, suppression of PTPA disrupts the assembly of PP2A heterotrimeric complexes, which leads to activation of these same oncogenic pathways. These observations delineate the PP2A family members and pathways perturbed by SV40ST during human cell transformation.