The machinery of translation is subject to regulation in situations of cellular determination, rapid response, and cellular stress. Translational initiation involves the recruitment of the 40S ribosomal subunit through elF2, elF3, and elF4 followed by the assembly of the function 80 complex. Dr. Dieter Wolf's lab identified distinct elF3 complexes containing either elF3m/Csn7B or the related elF3e/lnt6p (Zhou et al., 2005). Further studies support a hypothesis for the use of alternate versions of these elF3 complexes under conditions of stress in S. pombe. Using fission yeast as a model the experiments described in this proposal will test this hypothesis through identification and validation of translational targets of lnt6p-elF3e under conditions of stress. Candidates will be verified and analyzed by genetic and biochemical approaches to determine mechanisms of translational repression and activation. Significantly, reduced INT6 expression is also found in 30-40% of human breast cancers, suggesting a close link between loss of INT6 expression and breast cancer development. The proposed research explores a novel role of INT6 in tumorigenesis through basic studies of its involvement in stress-regulated translation. ? ? ?
