Reference: Zhao W, et al. (2020) Yeast MED2 is involved in the endoplasmic reticulum stress response and modulation of the replicative lifespan. Mech Ageing Dev 192:111381

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Abstract


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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Zhao W, Liu JX, Guo F, Liu XG
Primary Lit For
INO1 | HAC1 | IRE1 | MED2 | DNA-directed RNA polymerase II complex
Additional Lit For
KAR2 | EUG1 | FPR2 | PDI1 | ERO1 | LHS1

Gene Ontology Annotations 1 entry for 1 gene


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Gene/ComplexQualifierGene Ontology TermAnnotation ExtensionEvidenceSourceAssigned On
MED2acts upstream of or withinresponse to endoplasmic reticulum stressIMPSGD2021-02-12
Showing 1 to 1 of 1 entries

Phenotype Annotations 36 entries for 1 gene


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GenePhenotypeExperiment TypeMutant InformationStrain BackgroundChemicalDetails
MED2chemical compound accumulation: decreased
classical genetics overexpressionS288C reactive oxygen speciesDetails: 0.45-fold decrease in the generation or ROS relative to wt in unstressed cells
MED2chemical compound accumulation: decreased
classical genetics overexpressionS288C reactive oxygen speciesTreatment: tunicamycin, 1.5 μM
Details: 0.66-fold decrease in the generation or ROS relative to wt in tunicamycin stressed wt cells
MED2chemical compound accumulation: increased
classical genetics null
Allele: med2-Δ
S288C reactive oxygen speciesDetails: 2-fold increase in the generation or ROS relative to wt in unstressed cells
MED2chemical compound accumulation: increased
classical genetics null
Allele: med2-Δ
S288C reactive oxygen speciesTreatment: tunicamycin, 1.5 μM
Details: 2.17-fold increase in the generation or ROS relative to wt in tunicamycin stressed wt cells
MED2replicative lifespan: decreased
classical genetics null
Allele: med2-Δ
S288CDetails: RLS is 16% shorter in the null mutant relative to wt
MED2replicative lifespan: increased
classical genetics overexpressionS288CDetails: RLS is 12.5% longer relative to wt
MED2resistance to chemicals: decreased
classical genetics null
Allele: med2-Δ
S288C1.5 μM tunicamycinDetails: growth rate significantly lower than in tunicamycin treated wt cells
MED2resistance to chemicals: increased
classical genetics overexpressionS288C1.5 μM tunicamycinDetails: significantly higher resistance to ER stress relative to wt cells
MED2RNA accumulation: decreased
Reporter: ERO1 mRNA
classical genetics null
Allele: med2-Δ
S288C
MED2RNA accumulation: decreased
Reporter: ERO1 mRNA
classical genetics overexpressionS288C
Showing 1 to 10 of 36 entries