Mouse translation elongation factor eEF1A-2 interacts with Prdx-I to protect cells against apoptotic death induced by oxidative stress

eEF1A‐1 and eEF1A‐2 are two isoforms of translation elongation factor eEF1A. In adult mammalian tissues, isoform eEF1A‐1 is present in all tissues except neurons, cardiomyocytes, and myotubes, where its isoform, eEF1A‐2, is the only form expressed. Both forms of eEF1A have been characterized to function in the protein elongation step of translation, and eEF1A‐1 is shown to possess additional non‐canonical roles in actin binding/bundling, microtubule bundling/severing, and cellular transformation processes. To study whether eEF1A‐2 has similar non‐canonical functions, we carried out a yeast two‐hybrid screening using a full sequence of mouse eEF1A‐2 as bait. A total of 78 hits, representing 23 proteins, were identified and validated to be true positives. We have focused on the protein with the highest frequency of hits, peroxiredoxin I (Prdx‐I), for in‐depth study of its functional implication for eEF1A‐2. Here we show that Prdx‐I coimmunoprecipitates with eEF1A‐2 from extracts of both cultured cells and mouse tissues expressing this protein, but it does not do so with its isoform, eEF1A‐1, even though the latter is abundantly present. We also report that an eEF1A‐2 and Prdx‐I double transfectant increases resistance to peroxide‐induced cell death as high as 1 mM peroxide treatment, significantly higher than do single transfectants with either gene alone; this protection is correlated with reduced activation of caspases 3 and 8, and with increased expression of pro‐survival factor Akt. Thus, our results suggest that eEF1A‐2 interacts with Prdx‐I to functionally provide cells with extraordinary resistance to oxidative stress‐induced cell death. J. Cell. Biochem. 100: 267–278, 2007. © 2006 Wiley‐Liss, Inc.