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• W2094659875 abstract "Gα12, the α-subunit of the G12 family of heterotrimeric G proteins is involved in the regulation of cell proliferation and neoplastic transformation. GTPase-deficient, constitutively activated mutant of Gα12 (Gα12Q229L or Gα12QL) has been previously shown to induce oncogenic transformation of NIH3T3 cells promoting serum- and anchorage-independent growth. Reduced growth-factor dependent, autonomous cell growth forms a critical defining point at which a normal cell turns into an oncogenic one. To identify the underlying mechanism involved in such growth-factor/serum independent growth of Gα12QL-transformed NIH3T3, we carried out a two-dimensional differential proteome analysis of Gα12QL-transformed NIH3T3 cells and cells expressing vector control. This analysis revealed a total of 22 protein-spots whose expression was altered by more than 3-folds. Two of these spots were identified by MALDI−MS analysis as proliferating cell nuclear antigen (PCNA) and myeloid-leukemia-associated SET protein. The increased expressions of these proteins in Gα12QL cells were validated by immunoblot analysis. Furthermore, transient transfection studies with NIH3T3 cells indicated that the expression of activated Gα12 readily increased the expression of SET protein by 24 h. As SET has been previously reported to be an inhibitor of phosphatase PP2A, the nuclear phosphatase activity was monitored in cells expressing activated Gα12. Our results indicate that the nuclear phosphatase activity is inhibited by greater than 50% in Gα12QL cells compared to vector control cells. Thus, our results from differential proteome analysis presented here report for the first time a role for SET in Gα12-mediated signaling pathways and a role for Gα12 in the regulation of the leukemia-associated SET-protein expression. Keywords: G protein • Gα12 • SET • PP2A • PCNA • oncogene • cell transformation • cell proliferation" @default.
• W2094659875 created "2016-06-24" @default.
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• W2094659875 date "2004-10-16" @default.
• W2094659875 modified "2023-10-16" @default.
• W2094659875 title "Proteome Analysis of NIH3T3 Cells Transformed by Activated Gα12: Regulation of Leukemia-Associated Protein SET" @default.
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• W2094659875 doi "https://doi.org/10.1021/pr049896n" @default.
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