Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
Brenda J Andrews
Donnelly Center for Cellular and Biomolecular Research, Department of Medical Genetics, University of Toronto, Toronto, Canada
Charles Boone
Donnelly Center for Cellular and Biomolecular Research, Department of Medical Genetics, University of Toronto, Toronto, Canada; RIKEN Center for Sustainable Resource Science, Wako, Japan
Research Core for Interdisciplinary Sciences, Okayama University, Okayama, Japan; Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan
Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload.
