regulation of eIF2 alpha phosphorylation by dsRNA
Definition
Target type: biologicalprocess
Any process that modulates the rate, frequency, or extent of eIF2 alpha phosphorylation as a cellular response to double-stranded RNA. [GOC:dph, GOC:tb]
Double-stranded RNA (dsRNA) is a potent activator of the protein kinase R (PKR) pathway, a crucial component of the innate immune response to viral infections. PKR is a serine/threonine kinase that, upon activation by dsRNA, phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2α). This phosphorylation event has a profound impact on protein synthesis, leading to the shutdown of global translation.
The process begins with the recognition of dsRNA by PKR. PKR contains two dsRNA-binding domains (dsRBDs), which bind to the dsRNA molecule, triggering a conformational change in the kinase domain. This conformational change activates PKR's catalytic activity, allowing it to phosphorylate eIF2α.
eIF2α is a key component of the translation initiation complex. It acts as a guanine nucleotide exchange factor (GEF) for the small ribosomal subunit, promoting the binding of methionine-tRNA to the ribosome. Phosphorylation of eIF2α by PKR inhibits its GEF activity, leading to the accumulation of inactive eIF2α:GDP complexes. This accumulation effectively stalls the translation initiation process, preventing the assembly of new ribosomes on mRNA and halting protein synthesis.
The inhibition of protein synthesis by eIF2α phosphorylation plays a critical role in the antiviral response. By blocking viral protein production, the cell can effectively prevent the spread of the infection. Furthermore, the reduction in global protein synthesis allows the cell to conserve energy and resources for other cellular processes, such as the production of antiviral proteins.
In addition to its role in antiviral defense, the PKR-eIF2α pathway is also implicated in other cellular processes, including stress responses, apoptosis, and development. Dysregulation of this pathway has been linked to a variety of human diseases, including cancer and neurodegenerative disorders.
In summary, dsRNA-mediated activation of PKR leads to the phosphorylation of eIF2α, which in turn inhibits protein synthesis. This process is crucial for the antiviral response and plays a role in other cellular processes.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Nucleophosmin | A nucleophosmin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06748] | Homo sapiens (human) |
Compounds (6)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| imatinib | aromatic amine; benzamides; N-methylpiperazine; pyridines; pyrimidines | antineoplastic agent; apoptosis inducer; tyrosine kinase inhibitor | |
| pd 173955 | PD 173955: inhibits src family-selective tyrosine kinase; structure in first source | aryl sulfide; dichlorobenzene; methyl sulfide; pyridopyrimidine | tyrosine kinase inhibitor |
| ellagic acid | catechols; cyclic ketone; lactone; organic heterotetracyclic compound; polyphenol | antioxidant; EC 1.14.18.1 (tyrosinase) inhibitor; EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor; EC 2.4.1.1 (glycogen phosphorylase) inhibitor; EC 2.5.1.18 (glutathione transferase) inhibitor; EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor; EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor; EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; food additive; fungal metabolite; geroprotector; plant metabolite; skin lightening agent | |
| bosutinib | 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile: a Src kinase inhibitor; structure in first source | aminoquinoline; aromatic ether; dichlorobenzene; N-methylpiperazine; nitrile; tertiary amino compound | antineoplastic agent; tyrosine kinase inhibitor |
| crizotinib | crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER. | 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine | antineoplastic agent; biomarker; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
| ceritinib | ceritinib : A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the treatment of ALK-positive metastatic non-small cell lung cancer. ceritinib: an anaplastic lymphoma kinase inhibitor | aminopyrimidine; aromatic ether; organochlorine compound; piperidines; secondary amino compound; sulfone | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |