Target intelligence / Profile preview

Cytosolic 80S ribosome (80S ribosome)

Target
80S ribosome
Molecular classification
Enzyme, Other
01

Overview

The cytosolic 80S ribosome is the primary molecular machine responsible for protein synthesis in eukaryotic cells. It consists of two subunits: the large 60S subunit and the small 40S subunit, which together coordinate the translation of messenger RNA (mRNA) into polypeptide chains [Wikipedia]. Its primary biological function is the translation of genetic information from mRNA into functional proteins, a process involving initiation, elongation, and termination phases [Molecular Biology of the Cell]. In clinical medicine, the 80S ribosome is a therapeutic target for certain cancers; for instance, omacetaxine mepesuccinate binds to the ribosomal A-site to prevent the correct positioning of aminoacyl-tRNA, thereby inhibiting the synthesis of short-lived oncoproteins like BCR-ABL [PubChem, CID 23662344]. Furthermore, the 80S ribosome is the target of various ribosome-inactivating proteins (RIPs) such as ricin, which irreversibly damage the 28S rRNA, and certain antifungal agents that exploit structural differences between human and fungal ribosomes [PubMed, PMID 11433344]. Dysregulation of ribosomal biogenesis or function is associated with ribosomopathies and is often exploited by viruses to prioritize the translation of viral proteins over host proteins [Nature Reviews Genetics, 2019]. Because protein synthesis is essential for all living cells, drugs targeting the 80S ribosome often have a narrow therapeutic index and can cause significant systemic toxicity [StatPearls].

Other names
Eukaryotic ribosome80S ribosomal complexCytoplasmic ribosome
02

Mechanism of action

Omacetaxine mepesuccinate binds to the A-site of the 80S ribosome, preventing the initial elongation step of protein synthesis [FDA]. Ribosome-inactivating proteins like ricin depurinate the sarcin/ricin loop of the 28S rRNA, halting translation [PubMed, PMID 11433344].

03

Biological functions

Cell proliferationOther
04

Disease associations

CancerInfectionOther
05

Safety considerations

Myelosuppression [FDA]Gastrointestinal toxicity [FDA]General cytotoxicity due to non-selective inhibition of host protein synthesis [StatPearls]
06

Interacting drugs

Omacetaxine mepesuccinate

5 more in the full profile.

07

Biomarkers

Phosphorylated ribosomal protein S6 (p-S6) [PubMed, PMID 21860406]rRNA expression levels [PubMed, PMID 25236397]Polysome profile analysis [PubMed, PMID 21907144]

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