Matches in SemOpenAlex for { <https://semopenalex.org/work/W4238857652> ?p ?o ?g. }
Showing items 1 to 63 of
63
with 100 items per page.
- W4238857652 abstract "<p>Translation initiation has been identified as a therapeutic target for many diseases including cancers, Alzheimer’s disease, viral infections and cachexia. One protein involved in this process is the eukaryotic initiation factor 4A (eIF4A), an RNA helicase that is integral for cap-dependent translation initiation. Multiple drugs that inhibit the normal function of eIF4A have been identified, with one currently entering clinical trials. Recent investigations into the effects of eIF4A inhibitor treatment, however, have used concentrations that significantly hinder cell proliferation and survival. However, applications in Alzheimer’s disease, viral infections and cachexia require much lower inhibitor concentrations. Current evidence shows that under these conditions, inhibition of eIF4A leads to disruption of translation of individual transcripts in a manner that is dependent on their sequence and structure. However, the cell-wide effects of eIF4A inhibition at these low concentrations is still not known, and so the mechanisms through which treatments for these diseases will function are not fully elucidated. Using an expression-based analysis, we investigated the effects of mild perturbation of eIF4A through gene deletion mutations in yeast and low doses of the eIF4A inhibitor pateamine on human cells. With both these approaches we identify a range of expression changes in proteins throughout the proteostatic network, relating to processes such as translation, amino acid production, ribosome biogenesis, protein folding and protein degradation. Processes further removed from translation initiation were also found to be affected but differed between yeast and human cell line models, with energy metabolism being affected in yeast, and telomere maintenance and mRNA metabolism being affected in human cells. We also identified an mRNA 5′ untranslated region sequence that appears to confer a disproportionate reduction in expression only seen in pateamine treatment conditions. Through this approach we identify the key cellular effects of altered eIF4A function and demonstrate differences between reduced eIF4A function and pateamine inhibition.</p>" @default.
- W4238857652 created "2022-05-12" @default.
- W4238857652 creator A5047466461 @default.
- W4238857652 date "2021-12-08" @default.
- W4238857652 modified "2023-10-13" @default.
- W4238857652 title "Investigation of the Biological Effect of eIF4A Reduction and Inhibition" @default.
- W4238857652 doi "https://doi.org/10.26686/wgtn.17145923.v1" @default.
- W4238857652 hasPublicationYear "2021" @default.
- W4238857652 type Work @default.
- W4238857652 citedByCount "0" @default.
- W4238857652 crossrefType "dissertation" @default.
- W4238857652 hasAuthorship W4238857652A5047466461 @default.
- W4238857652 hasBestOaLocation W42388576521 @default.
- W4238857652 hasConcept C104317684 @default.
- W4238857652 hasConcept C105580179 @default.
- W4238857652 hasConcept C149364088 @default.
- W4238857652 hasConcept C161223559 @default.
- W4238857652 hasConcept C161295673 @default.
- W4238857652 hasConcept C2779419633 @default.
- W4238857652 hasConcept C3675279 @default.
- W4238857652 hasConcept C4718897 @default.
- W4238857652 hasConcept C5122226 @default.
- W4238857652 hasConcept C54355233 @default.
- W4238857652 hasConcept C62493599 @default.
- W4238857652 hasConcept C67705224 @default.
- W4238857652 hasConcept C86803240 @default.
- W4238857652 hasConcept C88478588 @default.
- W4238857652 hasConcept C95444343 @default.
- W4238857652 hasConcept C99348085 @default.
- W4238857652 hasConceptScore W4238857652C104317684 @default.
- W4238857652 hasConceptScore W4238857652C105580179 @default.
- W4238857652 hasConceptScore W4238857652C149364088 @default.
- W4238857652 hasConceptScore W4238857652C161223559 @default.
- W4238857652 hasConceptScore W4238857652C161295673 @default.
- W4238857652 hasConceptScore W4238857652C2779419633 @default.
- W4238857652 hasConceptScore W4238857652C3675279 @default.
- W4238857652 hasConceptScore W4238857652C4718897 @default.
- W4238857652 hasConceptScore W4238857652C5122226 @default.
- W4238857652 hasConceptScore W4238857652C54355233 @default.
- W4238857652 hasConceptScore W4238857652C62493599 @default.
- W4238857652 hasConceptScore W4238857652C67705224 @default.
- W4238857652 hasConceptScore W4238857652C86803240 @default.
- W4238857652 hasConceptScore W4238857652C88478588 @default.
- W4238857652 hasConceptScore W4238857652C95444343 @default.
- W4238857652 hasConceptScore W4238857652C99348085 @default.
- W4238857652 hasLocation W42388576521 @default.
- W4238857652 hasLocation W42388576522 @default.
- W4238857652 hasLocation W42388576523 @default.
- W4238857652 hasOpenAccess W4238857652 @default.
- W4238857652 hasPrimaryLocation W42388576521 @default.
- W4238857652 hasRelatedWork W2063058717 @default.
- W4238857652 hasRelatedWork W2161624752 @default.
- W4238857652 hasRelatedWork W2339627717 @default.
- W4238857652 hasRelatedWork W2787960267 @default.
- W4238857652 hasRelatedWork W2901551398 @default.
- W4238857652 hasRelatedWork W3038236348 @default.
- W4238857652 hasRelatedWork W3148897247 @default.
- W4238857652 hasRelatedWork W4225879951 @default.
- W4238857652 hasRelatedWork W4238857652 @default.
- W4238857652 hasRelatedWork W791565919 @default.
- W4238857652 isParatext "false" @default.
- W4238857652 isRetracted "false" @default.
- W4238857652 workType "dissertation" @default.