{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRIOK2 is an atypical protein kinase that plays a central role in ribosome biogenesis. In human cells, it is incorporated into late pre‐40S ribosomal particles and is essential for final cytoplasmic maturation steps. Its physical presence facilitates the release of trans‐acting factors (for example, hEnp1) from pre‐40S particles, while its kinase activity is required for recycling other factors (including hDim2, hLtv1, and hNob1) and proper processing of the 18S‐E pre‐rRNA. Moreover, phosphorylation of RIOK2 by kinases such as PLK1 and RSK links its function to cell cycle progression, particularly regulating the metaphase–anaphase transition, thereby coupling ribosome assembly with proliferative signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "Disruptions in RIOK2 regulation have been implicated in various cancers. Overexpression of RIOK2 is observed in glioblastoma, non‐small cell lung cancer, and tongue squamous cell carcinoma, where it contributes to oncogenesis by promoting cell growth, migration, invasion, and epithelial–mesenchymal transition. In these contexts, RIOK2 forms complexes with other key regulators (such as RIOK1 and mTOR components) and establishes feedforward loops that enhance Akt/mTOR signaling. Its expression is also negatively regulated by specific microRNAs (e.g. miR‑4744 and miR‑145), and structural studies reveal that RIOK2 dimerization can modulate its catalytic function. Furthermore, the discovery of selective small molecule ligands (e.g. diphenpyramide analogs) highlights RIOK2 as a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "Interestingly, beyond its role in ribosome maturation and tumorigenesis, RIOK2 has been recently characterized as a master transcriptional regulator in human hematopoietic cells. It harbors a winged helix-turn-helix DNA-binding domain and dual transactivation domains that drive erythroid differentiation while suppressing megakaryopoiesis and myelopoiesis, thereby coordinating human blood cell development. Expression levels of RIOK2 correlate with key hematopoietic transcription factors in several hematologic disorders, underscoring its potential as a therapeutic target for correcting defective hematopoiesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ivo Zemp, Thomas Wild, Marie-Françoise O'Donohue, et al. 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