ABSTRACT
The retrograde signaling pathway is well conserved from yeast to humans, which regulates cell adaptation during stress conditions and prevents cell death. One of its components, RTG1 encoded Rtg1p in association with Rtg3p communicates between mitochondria, nucleus, and peroxisome during stress for adaptation, by regulation of transcription. The F-box motif protein encoded by YDR131C constitutes a part of SCF Ydr131c -E3 ligase complex, with unknown function; however, it is known that retrograde signaling is modulated by the E3 ligase complex. This study reports epistasis interaction between YDR131C and RTG1, which regulates cell growth, response to genotoxic stress, decreased apoptosis, resistance to petite mutation, and cell wall integrity. The cells of ydr131cΔrtg1Δ genetic background exhibits growth rate improvement however, sensitivity to hydroxyurea, itraconazole antifungal agent and synthetic indoloquinazoline-based alkaloid (8-fluorotryptanthrin, RK64), which disrupts the cell wall integrity in Saccharomyces cerevisiae. The epistatic interaction between YDR131C and RTG1 indicates a link between protein degradation and retrograde signaling pathways.
Subject(s)
Apoptosis/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , DNA Damage/genetics , Epistasis, Genetic , F-Box Motifs/genetics , Gene Expression Regulation, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Signal Transduction/genetics , Acetic Acid/pharmacology , Antifungal Agents/pharmacology , Apoptosis/drug effects , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Cell Enlargement/drug effects , Cell Size/drug effects , DNA Damage/drug effects , Ethidium/pharmacology , Gene Deletion , Hydrogen Peroxide/pharmacology , Hydroxyurea/pharmacology , Itraconazole/pharmacology , Microorganisms, Genetically-Modified , Mutation/drug effects , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Sulfinic Acids/pharmacologyABSTRACT
Nonavailability of glucose as a carbon source results in glyoxylate pathway activation, which metabolizes nonfermentable carbon for energy generation in Saccharomyces cerevisiae. Ucc1p of S. cerevisiae inhibits activation of the glyoxylate pathway by targeting Cit2p, a key glyoxylate enzyme for ubiquitin-mediated proteasomal degradation when glucose is available as a carbon source. Sro9p, a La-motif protein involved in RNA biogenesis, interacts physically with the messenger RNA of UCC1; however, its functional relevance is yet to be discovered. This study presents binary epistatic interaction between UCC1 and SRO9, with functional implication on the growth rate, response to genotoxic stress, resistance to apoptosis, and petite mutation. Cells with ucc1Δsro9Δ, as their genetic background, exhibit alteration in morphology, improvement in growth rate, resistance to apoptosis, and petite mutation. Moreover, the study indicates a cross-link between ubiquitin-proteasome system and RNA biogenesis and metabolism, with applications in industrial fermentation and screening for cancer therapeutics.
