60S large ribosomal subunit (60S subunit)

The 60S large ribosomal subunit is the larger component of the eukaryotic 80S ribosome, serving as the catalytic heart of protein synthesis [7, 18]. It is composed of three ribosomal RNA (rRNA) strands (28S, 5.8S, and 5S) and approximately 47 to 49 ribosomal proteins, which together form the peptidyl transferase center (PTC) and the peptide exit tunnel [7, 14, 18, 22]. The 60S subunit is essential for translating messenger RNA into functional proteins, a process frequently hijacked or upregulated in malignant cells to support rapid proliferation [2, 19]. Therapeutically, the 60S subunit is targeted by inhibitors like omacetaxine mepesuccinate, which binds to the A-site to block translation elongation, particularly affecting short-lived oncoproteins like Bcr-Abl and Mcl-1 [1, 2, 3]. Beyond its role in translation, components of the 60S subunit participate in extra-ribosomal signaling pathways, such as the regulation of the p53 tumor suppressor via the RPL5/RPL11-MDM2 axis, making it a critical node in both cellular metabolism and oncology [8, 12, 13, 20]. Polysomes, which are clusters of multiple ribosomes translating a single mRNA strand, represent the active functional state of this target in the cytoplasm [4, 11].

Other names

Large ribosomal subunitEukaryotic 60S ribosomal subunitLSUPolyribosomePolysome80S ribosome large subunit

Omacetaxine mepesuccinate binds specifically to the A-site cleft in the peptidyl-transferase center of the 60S ribosomal subunit, sterically hindering the positioning of aminoacyl-tRNAs and thereby preventing the initial elongation step of protein synthesis [1, 2, 3, 4].