Target intelligence / Profile preview

Eukaryotic cytosolic 80S ribosome (80S ribosome)

Target
80S ribosome
Molecular classification
Ribonucleoprotein complex, Enzyme, Translation machinery
01

Overview

The eukaryotic cytosolic 80S ribosome is the primary molecular machinery responsible for protein synthesis in the cytoplasm of eukaryotic cells [1.2.1, 1.5.1]. It is a massive ribonucleoprotein complex composed of two subunits: the small 40S subunit (containing 18S rRNA and approximately 33 proteins) and the large 60S subunit (containing 28S, 5.8S, and 5S rRNAs and approximately 47 proteins) [1.3.2, 1.5.1]. The ribosome facilitates the translation of genetic information from messenger RNA (mRNA) into functional proteins through a coordinated cycle of initiation, elongation, termination, and recycling [1.4.1, 1.4.2]. In many diseases, particularly cancer, ribosome biogenesis and translation rates are significantly upregulated to support the high biomass requirements of rapidly proliferating cells [1.2.2, 1.3.2]. Drugs such as omacetaxine mepesuccinate (homoharringtonine) target the 80S ribosome by binding to the A-site cleft, thereby inhibiting the elongation phase of translation and preferentially reducing the levels of short-lived oncogenic proteins like BCR-ABL, MYC, and MCL1 [1.6.2, 1.6.3]. While the ribosome is a validated therapeutic target in hematological malignancies, its essential role in all cells presents challenges regarding systemic toxicity and myelosuppression [1.3.5, 1.6.1].

Other names
Human 80S ribosomeCytosolic ribosomeEukaryotic ribosome80S translation machinery80S translation complex
02

Mechanism of action

Inhibition of protein synthesis by binding to functional sites such as the A-site cleft, peptidyl transferase center (PTC), or peptide exit tunnel (PET), thereby blocking translation elongation, initiation, or termination.

03

Biological functions

Protein synthesismRNA translationPeptidyl transferase activitymRNA decodingRibosome recycling
04

Disease associations

CancerRibosomopathyViral infectionGenetic diseaseInfection
05

Safety considerations

MyelosuppressionThrombocytopeniaNeutropeniaRibotoxic stress responseSystemic cytotoxicityOff-target effects on mitochondrial ribosomes
06

Interacting drugs

Omacetaxine mepesuccinate

9 more in the full profile.

07

Biomarkers

BCR-ABL1 T315I mutationc-MYC protein levelsMCL1 protein levelsRibosome biogenesis rateNucleolar size

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