Heavy metal pollution is one of the most severe environmental problem. The toxicity of heavy metals is correlated with the production of increased reactive oxygen species and misfolded protein accumulation. Exposures of these metals even at low concentrations adversely affect human health. The Tup1-Cyc8 complex has been identified as a general repressor complex, is also involved in the derepression of few target genes in association with gene-specific activator proteins. Exposure to heavy metals activates the antioxidant defense mechanism, essential for cellular homeostasis. Here we present evidence that TUP1/CYC8 deleted cells are compromised to tolerate heavy metals exposure. Upon metal-induced oxidative stress, Yeast AP-1p (Yap1) recruits the Tup1-Cyc8 complex to the promoter of oxidative stress response gene GSH1 and derepresses its expression. We also found that the TUP1/CYC8 deficient cells have altered endoplasmic reticulum (ER) homeostasis and fail to activate the unfolded protein response pathway. In response to ER stress, the Tup1-Cyc8 complex, with the help of activated Hac1, binds to the promoter of ER chaperone KAR2 and activates its transcription. Altogether, our findings suggest that the Tup1-Cyc8 complex is crucial for the activation of genes that are involved in the mitigation of oxidative and ER stress during heavy metal exposure.

• PMID: 35123133
• DOI full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Kumawat R, Tomar RS

Primary Lit For

Additional Lit For

Review For