Target type: biologicalprocess
Any process that stops, prevents or reduces the rate of translation as a result of a stimulus indicating the organism is under stress. [GOC:mah]
Negative regulation of translation in response to stress is a critical cellular process that allows organisms to adapt to adverse environmental conditions. When cells encounter stress, such as nutrient deprivation, heat shock, or oxidative stress, they activate mechanisms to suppress protein synthesis, thereby conserving resources and preventing the production of potentially harmful proteins. This process involves a complex interplay of signaling pathways, regulatory proteins, and modifications to mRNA transcripts.
One key mechanism involves the activation of the integrated stress response (ISR), a signaling pathway that is triggered by various stressors. The ISR involves the phosphorylation of eukaryotic initiation factor 2α (eIF2α), a critical component of the translation initiation machinery. Phosphorylation of eIF2α reduces its ability to deliver initiator methionine tRNA (Met-tRNAi) to the ribosome, leading to a global decrease in translation initiation.
Another important aspect of negative regulation of translation in response to stress is the control of mRNA stability and translation efficiency. Stress conditions often lead to the degradation of mRNAs encoding proteins that are not essential for survival or that could exacerbate the stress response. This degradation is mediated by RNA-binding proteins and microRNAs that target specific mRNA sequences.
Furthermore, stress can induce changes in the cellular localization of mRNAs, leading to their sequestration in cytoplasmic granules or their relocation to specific cellular compartments. These changes can influence the accessibility of mRNAs to ribosomes and ultimately affect translation efficiency.
In addition to the ISR and mRNA stability regulation, stress can also influence translation initiation through the modulation of cap-dependent and cap-independent translation initiation pathways. These pathways utilize different mechanisms to recruit ribosomes to the 5' end of mRNAs, and their relative activity can be altered under stress conditions.
In conclusion, negative regulation of translation in response to stress is a multifaceted process involving multiple signaling pathways, regulatory proteins, and post-transcriptional modifications. This intricate network allows cells to efficiently shut down protein synthesis in response to various stressors, ensuring survival and preserving cellular homeostasis.'
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Protein | Definition | Taxonomy |
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Eukaryotic translation initiation factor 2-alpha kinase 3 | A eukaryotic translation initiation factor 2-alpha kinase 3 that is encoded in the genome of human. [PRO:CNx, UniProtKB:Q9NZJ5] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
entrectinib | entrectinib : A member of the class of indazoles that is 1H-indazole substituted by [4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzoyl]amino and 3,5-difluorobenzyl groups at positions 3 and 5, respectively. It is a potent inhibitor of TRKA, TRKB, TRKC, ROS1, and ALK (IC50 values of 0.1 to 1.7 nM), and used for the treatment of NTRK, ROS1 and ALK gene fusion-positive solid tumours. entrectinib: inhibits TRK, ROS1, and ALK receptor tyrosine kinases; structure in first source | benzamides; difluorobenzene; indazoles; N-methylpiperazine; oxanes; secondary amino compound; secondary carboxamide | antibacterial agent; antineoplastic agent; apoptosis inducer; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
nms p937 | NMS P937: a polo-like kinase 1 inhibitor; structure in first source | ||
nms-p118 | NMS-P118: a PARP-1 inhibitor; structure in first source | ||
gsk2656157 | biaryl; indoles; methylpyridines; organofluorine compound; pyrrolopyrimidine; tertiary carboxamide | antineoplastic agent; EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor; PERK inhibitor | |
7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1h-indol-5-yl)-7h-pyrrolo(2,3-d)pyrimidin-4-amine | 7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine: inhibits protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK); structure in first source | ||
nms-e973 | NMS-E973: structure in first source |