Target intelligence / Profile preview

Eukaryotic 80S cytosolic ribosome (80S ribosome) (80S ribosome)

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

Overview

The eukaryotic 80S cytosolic ribosome is a massive ribonucleoprotein complex that serves as the primary site of protein synthesis in eukaryotic cells [Khatter et al., Nature, 2015]. Composed of a small 40S subunit and a large 60S subunit, it facilitates the translation of genetic information from messenger RNA (mRNA) into functional polypeptides [UniProt]. This process involves complex interactions between ribosomal RNA (rRNA), ribosomal proteins, transfer RNA (tRNA), and various translation factors. Beyond its fundamental role in cellular physiology, the 80S ribosome is implicated in several diseases; mutations in ribosomal proteins or assembly factors cause ribosomopathies like Diamond-Blackfan anemia [Narla & Ebert, Blood, 2010], and its upregulation is a hallmark of many cancers. While many antibiotics specifically target the bacterial 70S ribosome, the 80S ribosome is the target of potent toxins like ricin and therapeutic agents such as omacetaxine mepesuccinate, which is used to treat certain leukemias by inhibiting protein synthesis [Gandhi et al., 2014]. Understanding the 80S ribosome's structure and function is crucial for developing selective inhibitors that can distinguish between host and pathogen ribosomes or target the hyperactive translation machinery in malignant cells [Pelletier et al., Nature Reviews Drug Discovery, 2015].

Other names
Cytosolic ribosomeEukaryotic ribosome80S ribonucleoprotein complex80S cytosolic ribosome
02

Mechanism of action

Inhibition of translation initiation and elongation by binding to ribosomal subunits (e.g., the A-site) or enzymatically modifying ribosomal RNA (e.g., depurination of the sarcin/ricin loop) [Gandhi et al., 2014; Sandvig & van Deurs, 2002].

03

Biological functions

Protein biosynthesis [UniProt]Translation [Khatter et al., Nature, 2015]Peptidyl transferase activity [Nissen et al., Science, 2000]mRNA decoding [Khatter et al., Nature, 2015]Other
04

Disease associations

Cancer [Pelletier et al., Nature Reviews Drug Discovery, 2015]Infection [Walsh & Mohr, Microbiology and Molecular Biology Reviews, 2011]Ribosomopathy [Narla & Ebert, Blood, 2010]Other
05

Safety considerations

Systemic toxicity [Pelletier et al., 2015]Bone marrow suppression [Synribo Prescribing Information]Narrow therapeutic index [Gandhi et al., 2014]Off-target effects on mitochondrial ribosomes [Böttger et al., 2013]
06

Interacting drugs

Omacetaxine mepesuccinate [FDA, 2012]

6 more in the full profile.

07

Biomarkers

RPS19 [Narla & Ebert, Blood, 2010]RPL5 [Narla & Ebert, Blood, 2010]RPL11 [Narla & Ebert, Blood, 2010]28S rRNA levels18S rRNA levels

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