Right open reading frame kinase 2 (RIOK2)

Right open reading frame kinase 2 (RIOK2) is an atypical serine/threonine kinase that serves as a crucial factor in the maturation of the 40S ribosomal subunit (UniProt Q9BVS4). It primarily functions in the late stages of pre-40S assembly, facilitating the transition of ribosomal particles from the nucleus to the cytoplasm (PubMed: 25126786). RIOK2 is frequently overexpressed in various malignancies, including glioblastoma and pancreatic cancer, where it promotes tumor cell survival and proliferation by integrating ribosome biogenesis with oncogenic signaling pathways like PI3K/AKT (PubMed: 23619167). As a metabolic checkpoint, it ensures that protein synthesis capacity matches the demands of rapidly dividing cancer cells. While no RIOK2-targeted therapies are currently FDA-approved, small-molecule inhibitors are being explored in preclinical studies to disrupt its kinase activity and induce proteotoxic stress in cancer cells (PubMed: 30104378). The therapeutic challenge lies in targeting RIOK2 specifically enough to avoid disrupting essential protein synthesis in healthy tissues.

Other names

RIO kinase 2Serine/threonine-protein kinase RIO2RIOK2

Inhibition of the atypical kinase activity of RIOK2, leading to the disruption of 40S ribosomal subunit maturation and subsequent cell cycle arrest or apoptosis.