Actin represents one of the most abundant and extensively studied proteins found in eukaryotic cells. It has been identified as a major target for destruction during the process of apoptosis. Recent research has also highlighted a role for cytoskeletal components in the initiation and inhibition of apoptotic processes. The high degree of conservation that exists between actins from divergent eukaryotes, particularly with respect to those that contribute to the cytoskeleton, has meant that functional studies from the model yeast Saccharomyces cerevisiae have proven useful in elucidating its cellular roles. Within the context of apoptosis in yeasts, actin seems to function as part of the signalling mechanisms that link nutritional sensing to a mitochondrialdependent commitment to cell death. Studies in yeasts have also shown that oxidative damage accrued by the actin cytoskeleton is closely monitored and is tethered to an apoptotic response. Strong, but as yet, undefined links between the actin cytoskeleton and apoptosis have also been described in studies from plant and animal systems. The widespread involvement of actin in apoptotic mechanisms from diverse eukaryotic organisms raises the possibility of conserved regulatory pathways, further strengthening the relevance of yeast research in this area.
The translation elongation factor eEF1A is one of the most abundant proteins found within cells, and its role within protein synthesis is well documented. Levels of eEF1A are tightly controlled, with inappropriate expression linked to oncogenesis. However, the mechanisms by which increased eEF1A expression alters cell behaviour are unknown. Our analyses in yeast suggest that elevation of eEF1A levels leads to stabilisation of the spindle pole body and changes in nuclear organisation. Elevation of the eEF1A2 isoform also leads to altered nuclear morphology in cultured human cells, suggesting a conserved role in maintaining genome stability. Gene expression and metabolomic analyses reveal that the level of eEF1A is crucial for the maintenance of metabolism and amino acid levels in yeast, most likely because of its role in the control of vacuole function. Increased eEF1A2 levels trigger lysosome biogenesis in cultured human cells, also suggesting a conserved role within metabolic control mechanisms. Taken together, our data suggest that the control of eEF1A levels is important for the maintenance of a number of cell functions beyond translation and that its de-regulation might contribute to its oncogenic properties.
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