减压
雅普1
细胞生物学
激活剂(遗传学)
抑制因子
氧化应激
转录因子
未折叠蛋白反应
内质网
生物
化学
生物化学
基因表达
基因
心理压抑
作者
Ramesh Kumawat,Raghuvir Singh Tomar
标识
DOI:10.1016/j.jhazmat.2022.128367
摘要
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.
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