Force expression of a mutated IMPDH2, lacking the MPA-binding site, results in resistance to MPA. (A) An IMPDH2 variant having normal IMP hydrogenase activity but lacking the MPA-binding site was fused to a GFP reporter (mutIMPDH2) and expressed in HeLa cells by a lentiviral vector. FACS analysis showed robust GFP expression in the transduced HeLa cells, but not in mock-transduced cells. Transduced cells appear to be resistant to MPA both in (B) colony formation (mean ± SD, n = 6, **P < 0.01) and (C) cell proliferation assays (mean ± SEM, n = 30, ***P < 0.001). (D) MPA-mediated induction of early apoptotic cells, as well as late apoptotic cells, is reduced significantly in mutIMPDH2 HeLa cells (mean ± SD, n = 3. *P < 0.05; **P < 0.01).