Target intelligence / Profile preview

Eukaryotic translation machinery (80S ribosome) (80S ribosome)

Target
80S ribosome
Molecular classification
Ribonucleoprotein complex, Enzyme, Macromolecular machine
01

Overview

The eukaryotic translation machinery is the complex macromolecular apparatus responsible for protein synthesis, comprising the 80S ribosome (composed of 40S and 60S subunits) and various auxiliary proteins known as translation factors [Source: NIH/NCBI]. This machinery decodes genetic information from mRNA into functional polypeptides, a process essential for cellular growth, differentiation, and homeostasis. In many diseases, particularly cancer and viral infections, this machinery is hijacked or dysregulated to favor the production of oncogenic or viral proteins over host cell maintenance [Source: PubMed, Nature]. For instance, viruses like SARS-CoV-2 rely entirely on the host's ribosomes for replication, while many tumors overexpress initiation factors like eIF4E to drive proliferation [Source: Science, Journal of Clinical Oncology]. Consequently, components of this machinery have become significant therapeutic targets, with drugs like zotatifin and plitidepsin designed to disrupt specific stages of the translation cycle. However, because protein synthesis is a fundamental biological process, targeting it requires high specificity to avoid severe systemic toxicity and maintain a viable therapeutic index [Source: Nature Reviews Drug Discovery].

Other names
Host ribosomeTranslational apparatusProtein synthesis machineryEukaryotic translation system80S ribosome complex
02

Mechanism of action

Inhibition of protein synthesis by targeting various stages of translation, including initiation (e.g., eIF4A/eIF4E inhibition), elongation (e.g., eEF1A inhibition), or the ribosome's peptidyl transferase center [Source: Nature, Science].

03

Biological functions

Protein synthesisTranslation initiationTranslation elongationTranslation terminationProteostasis
04

Disease associations

InfectionCancerRibosomopathyNeurodegenerative disease
05

Safety considerations

Systemic toxicityNarrow therapeutic indexMyelosuppressionGastrointestinal toxicityPotential for off-target effects on mitochondrial ribosomes
06

Interacting drugs

Zotatifin

7 more in the full profile.

07

Biomarkers

eIF4E expression levelsPhosphorylated 4E-BP1 (p-4E-BP1)Ribosomal protein S6 phosphorylationGlobal protein synthesis rate (e.g., puromycin incorporation)

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