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J. Biol. Chem., Vol. 277, Issue 8, 6080-6087, February 22, 2002

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The Interferon (IFN)-induced GTPase, mGBP-2
ROLE IN IFN--INDUCED MURINE FIBROBLAST PROLIFERATION^*

Victoria Y. Gorbacheva, Daniel Lindner^§, Ganes C. Sen, and Deborah J. Vestal^¶

From the  Department of Molecular Biology of the Lerner Research Institute and the ^§ Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

To investigate the function of mGBP-2, a member of the interferon (IFN)-induced guanylate-binding protein family of GTPases, NIH 3T3 fibroblasts were generated that constitutively expressed mGBP-2. mGBP-2 induced a faster growth rate, with the highest expressing clones showing approximately a 50% reduction in doubling time. mGBP-2-expressing cells also grew to higher density and exhibited partial loss of contact growth inhibition, as evidenced by the formation of foci in post-confluent cultures. In addition, mGBP-2-expressing cells showed decreased dependence on serum-derived growth factors. However, they did not lose the requirement for anchorage-dependent growth. Finally, NIH 3T3 cells expressing mGBP-2 formed tumors in athymic mice. An mGBP-2 protein carrying a point mutation (S52N) that reduced GTP binding failed to produce these phenotypes when expressed at the same levels as wild type. The additional finding that IFN- treatment of NIH 3T3 cells resulted in an increase in proliferation similar to that observed for mGBP-2 in the absence of other IFN-induced proteins suggests that mGBP-2 may indeed be important for these growth changes.

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