Saccharomyces cerevisiae MED2/YDL005C is a subunit of the mediator complex (Mediator), which is responsible for tightly controlling the transcription of protein-coding genes by mediating the interaction of RNA polymerase II with gene-specific transcription factors. Although a high-throughput analysis in yeast showed that the MED2 protein exhibits altered cellular localization under hypoxic stress, no specific function of MED2 has been described to date. In this study, we first provided evidence that MED2 is involved in the endoplasmic reticulum (ER) stress response and modulation of the replicative life span. We showed that deletion of MED2 leads to sensitivity to the ER stress inducer tunicamycin (TM) as well as a shortened replicative lifespan (RLS), accompanied by increased intracellular ROS levels and hyperpolarization of mitochondria. On the other hand, overexpression of MED2 in wild-type (WT) yeast enhanced TM resistance and extended the RLS. In addition, the IRE1-HAC1 pathway was essential for the TM resistance of MED2-overexpressing cells. Moreover, we showed that MED2 deficiency enhances ER unfolded protein response (UPR) activity compared to that in WT cells. Collectively, these results suggest the novel role of MED2 as a regulator in maintaining ER homeostasis and longevity.
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.
| Gene | Phenotype | Experiment Type | Mutant Information | Strain Background | Chemical | Details |
|---|---|---|---|---|---|---|
| MED2 | chemical compound accumulation: decreased | classical genetics | overexpression | S288C | reactive oxygen species | Details: 0.45-fold decrease in the generation or ROS relative to wt in unstressed cells |
| MED2 | chemical compound accumulation: decreased | classical genetics | overexpression | S288C | reactive oxygen species | Treatment: tunicamycin, 1.5 μM Details: 0.66-fold decrease in the generation or ROS relative to wt in tunicamycin stressed wt cells |
| MED2 | chemical compound accumulation: increased | classical genetics | null Allele: med2-Δ | S288C | reactive oxygen species | Details: 2-fold increase in the generation or ROS relative to wt in unstressed cells |
| MED2 | chemical compound accumulation: increased | classical genetics | null Allele: med2-Δ | S288C | reactive oxygen species | Treatment: tunicamycin, 1.5 μM Details: 2.17-fold increase in the generation or ROS relative to wt in tunicamycin stressed wt cells |
| MED2 | replicative lifespan: decreased | classical genetics | null Allele: med2-Δ | S288C | Details: RLS is 16% shorter in the null mutant relative to wt | |
| MED2 | replicative lifespan: increased | classical genetics | overexpression | S288C | Details: RLS is 12.5% longer relative to wt | |
| MED2 | resistance to chemicals: decreased | classical genetics | null Allele: med2-Δ | S288C | 1.5 μM tunicamycin | Details: growth rate significantly lower than in tunicamycin treated wt cells |
| MED2 | resistance to chemicals: increased | classical genetics | overexpression | S288C | 1.5 μM tunicamycin | Details: significantly higher resistance to ER stress relative to wt cells |
| MED2 | RNA accumulation: decreased Reporter: ERO1 mRNA | classical genetics | null Allele: med2-Δ | S288C | ||
| MED2 | RNA accumulation: decreased Reporter: ERO1 mRNA | classical genetics | overexpression | S288C |