response to cycloheximide

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cycloheximide stimulus. Cycloheximide (actidione) is an antibiotic produced by some Streptomyces species which interferes with protein synthesis in eukaryotes. [GOC:ef, ISBN:0198506732]

Cycloheximide is a potent inhibitor of eukaryotic protein synthesis, specifically targeting the peptidyl transferase center of the 80S ribosome. This inhibition disrupts the formation of peptide bonds, effectively halting translation and preventing the synthesis of new proteins. The response to cycloheximide involves a complex interplay of cellular processes that aim to mitigate the effects of translation arrest and restore cellular homeostasis.

Upon cycloheximide exposure, cells rapidly exhibit a decrease in protein synthesis rates. This is a direct consequence of the drug's inhibition of the ribosome. The cessation of protein synthesis leads to a decline in the production of essential cellular components, including enzymes, structural proteins, and regulatory factors. This disruption in protein synthesis has far-reaching consequences for cellular function and survival.

To cope with the inhibition of protein synthesis, cells employ a range of adaptive mechanisms. One key response is the activation of stress response pathways, including the unfolded protein response (UPR) and the integrated stress response (ISR). The UPR is triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which occurs when protein synthesis is impaired. Activation of the UPR leads to a cascade of signaling events that aim to alleviate ER stress and restore protein folding capacity. These events include the upregulation of chaperone proteins that assist in protein folding, the downregulation of protein translation to reduce the burden on the ER, and the activation of the ER-associated protein degradation (ERAD) pathway to remove misfolded proteins.

The ISR, also known as the eIF2α kinase pathway, is another important stress response pathway that is activated by cycloheximide. The ISR is triggered by the accumulation of uncharged tRNA molecules, which occurs when protein synthesis is inhibited. Activation of the ISR leads to the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), which inhibits the initiation of translation. This inhibition of translation further reduces the burden on the ER and conserves cellular resources.

In addition to activating stress response pathways, cells may also undergo changes in gene expression in response to cycloheximide exposure. These changes in gene expression can be either direct or indirect, with the former being caused by the binding of cycloheximide to specific transcription factors, and the latter being caused by the activation of stress response pathways. Some genes that are commonly upregulated in response to cycloheximide exposure include genes involved in protein degradation, stress response, and cell cycle arrest.

The response to cycloheximide can vary depending on the cell type and the concentration of the drug. At low concentrations, cycloheximide may induce a reversible inhibition of protein synthesis, while at higher concentrations, it can lead to cell death. The specific effects of cycloheximide on different cell types are influenced by a variety of factors, including the cell's metabolic state, the expression levels of specific proteins, and the presence of other stressors.

In summary, the biological response to cycloheximide is a complex process that involves a combination of direct effects on protein synthesis and indirect effects mediated by stress response pathways and changes in gene expression. The precise nature of this response can vary depending on the cell type and the concentration of the drug.'
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Proteins (2)

Compounds (45)