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Heterologous expression of human phosphodiesterase 3A enhances oxidative stress resistance in yeast
Author(s) -
Rhee Dong Keun,
Lim Jung Chae,
Hockman Steven C.,
Ahmad Faiyaz,
Manganiello Vincent C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1052.1
Subject(s) - yap1 , yeast , microbiology and biotechnology , oxidative stress , saccharomyces cerevisiae , biology , heterologous expression , signal transduction , ubiquitin ligase , chemistry , biochemistry , gene , ubiquitin , transcription factor , recombinant dna
All organisms have evolved to overcome environmental stress via protective antioxidant activity, which slows ageing or senescence and extends life. cAMP/PKA signaling pathways are directly related to increased resistance to H2O2 and to the extension of life span in yeast cells. PDEs control cAMP pools that are involved in regulating the cell cycle, and they are components of the RAS/cAMP pathway that mediates general stress responses. Using the yeast two‐hybrid system to study the interaction of human PDE3A (hPDE3A) and human RMND5A (hRMND5A), a E3 ubiquintin ligase, we noticed that expression of hPDE3A and an ubiquitinylation site mutant K13R hPDE3A (which did not interact with hRMND5A) altered yeast growth in response to environmental stresses. For our current studies we therefore used S. cerevisiae as a model system to study effects of exogenous WT hPDE3A and on H2O2‐mediated stress responses in yeast. Our results suggest that hPDE3A enhances calcineurin activity and upregulates YAP1 and YAP1‐dependent gene expression, which in turn leads to increased expression of cellular target genes involved in recovery from oxidative stress, including up‐regulation of SRX1 and resulting in reduction of Tsa1p.