Phosphorylation of p53 at serine 46 (S46) is essential for counteracting Zfra-mediated cell death. COS7 cells were co-transfected with both p53 and/or Zfra by electroporation, followed by culturing for 24 hr and then determining the extent of cell death by staining with crystal violet. In addition, the cells were also introduced with mutants of p53 (S46) and/or Zfra(S8G). The results show that p53 and Zfra nullified each other's activity in causing cell death (n = 8, mean ± standard deviation). The apoptotic function of both Zfra(S8G) and p53(S46G) was significantly reduced. S8G mutant had no effect in reducing p53-mediated cell death.