ATM and ATR are not mutually required for inhibition of their signaling pathways by E4orf4.

(A) ATM-deficient A-T fibroblasts and matching WT fibroblasts were either mock-infected or infected with the Ad mutants dl366* and dl366*+E4orf4. Proteins were harvested 24 hrs later and Western blot analysis was carried out with the indicated antibodies. Quantitation and normalization were performed as described in the legend to Fig 1. (B) Clone 13 cells expressing E4orf4 under Dox regulation were induced for 3 hrs (+) or were left uninduced (-). They were then treated with NCS for one hr in the presence or absence of an ATM inhibitor (ATMi: KU60019). Protein extracts were subjected to Western blot analysis with the indicated antibodies. Quantitation and normalization were performed as described in the legend to Fig 1. (C) HeLa cells were either mock-infected or infected with the Ad mutants dl366* and dl366*+E4orf4. An ATR inhibitor (ATRi: ETP46464) was added to the infected cells and another group of infected cells was left untreated (-). Proteins were harvested 24 hrs post infection and Western blot analysis was carried out with the indicated antibodies. (D) The intensities of protein bands in Western blots from two independent experiments performed as described in C were quantified by densitometry. Relative pATM-S1981 levels were calculated as described in the legend to Fig 1, and the average of the two experiments is shown in the graph. Error bars represent standard error of the mean and statistical significance was determined using a paired student t test. *: p