Regulation of organelle size, composition, and location within eukaryotic cells is essential to cellular homeostasis in health, and is often aberrant in disease. A growing body of evidence indicates that ubiquitination of proteins is a multifunctional signal involved not only in protein degradation, but also in a diversity of cell signaling events. The objective of this research is to investigate the role of ubiquitination in regulation of endoplasmic reticulum structure by studying the formation of HMG-CoA reductase-inducible membranes, called karmellae, in the yeast Saccharomyces cerevisiae. Experiments described in this proposal are based on a previous observation that yeast deletion mutants lacking Ubc7p, a ubiquitin conjugating enzyme known to be involved in ER-associated degradation, exhibits decreased growth in the presence of increased levels of HMG-CoA reductase. Genetic screens, biochemical assays and microscopy will be used to assess the impact ubiquitination has on membrane biogenesis in wildtype yeast strains and yeast strains lacking Ubc7p. Completion of this research will not only identify the specific role of Ubc7p in modulating karmellae formation in yeast, but also could uncover a general role for ubiquitination in organelle biogenesis.
| Loertscher, Jennifer; Larson, Lynnelle L; Matson, Clinton K et al. (2006) Endoplasmic reticulum-associated degradation is required for cold adaptation and regulation of sterol biosynthesis in the yeast Saccharomyces cerevisiae. Eukaryot Cell 5:712-22 |
