Target intelligence / Profile preview

Eukaryotic ribosome and translation elongation machinery (80S ribosome/eEFs)

Target
80S ribosome/eEFs
Molecular classification
Ribonucleoprotein complex, Enzyme, GTPase, Other
01

Overview

The eukaryotic ribosome and translation elongation machinery constitute the central apparatus for protein synthesis in eukaryotic cells (Alberts et al., Molecular Biology of the Cell). This complex system includes the 80S ribosome, composed of 40S and 60S subunits, and essential accessory proteins known as eukaryotic translation elongation factors (eEFs), such as eEF1A and eEF2 (UniProt P68104, P13639). During the elongation phase, the machinery decodes mRNA sequences into polypeptide chains through a cycle of aminoacyl-tRNA binding, peptide bond formation, and translocation (PubMed PMID: 25103185). Because rapidly proliferating cells, such as cancer cells, exhibit a high demand for protein synthesis, this machinery is a critical therapeutic target. Drugs like omacetaxine mepesuccinate inhibit the elongation process by binding to the A-site of the 60S subunit to treat chronic myeloid leukemia (PubMed PMID: 23070353). Other agents, such as ataluren, modulate the ribosome to bypass premature stop codons in genetic disorders like Duchenne muscular dystrophy (EMA/Translarna). However, targeting such a fundamental cellular process requires careful management to avoid systemic toxicity and damage to healthy tissues (PubMed PMID: 28655771).

Other names
80S ribosomeProtein synthesis machineryTranslation apparatusEukaryotic translation elongation factorsRibosomal protein complex
02

Mechanism of action

Inhibition of aminoacyl-tRNA binding to the ribosomal A-site, inhibition of peptidyl transferase activity within the 60S subunit, inhibition of ribosomal translocation along mRNA mediated by eEF2, and induction of translational read-through of premature stop codons (PubMed PMID: 23070353, PubMed PMID: 25103185).

03

Biological functions

Protein synthesisTranslation elongationPeptide bond formationTranslocationmRNA decoding
04

Disease associations

CancerInfectionGenetic disorderRibosomopathyInflammation
05

Safety considerations

MyelosuppressionGastrointestinal toxicityGeneral cytotoxicity due to inhibition of essential cellular processesNarrow therapeutic windowPotential cross-reactivity with mitochondrial ribosomes
06

Interacting drugs

Omacetaxine mepesuccinate

6 more in the full profile.

07

Biomarkers

eEF2 phosphorylation statusGlobal protein synthesis rate (OPP labeling)Ribosomal protein expression levelsp70S6K activity4E-BP1 phosphorylation

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