Ribosomal oxygenase 1 (RIOX1) (RIOX1)

Ribosomal oxygenase 1 (RIOX1), also known as Nucleolar protein 66 (NO66), is a dual-function enzyme that plays a pivotal role in both ribosome biogenesis and epigenetic regulation (UniProt Q9H6W3). It belongs to the JmjC domain-containing family of 2-oxoglutarate-dependent dioxygenases and is primarily localized within the nucleolus and nucleoplasm (PubMed: 23103944). RIOX1 catalyzes the β-hydroxylation of histidine residues in the 60S ribosomal protein L8 (RPL8) and acts as a histone lysine demethylase targeting H3K4 and H3K36 marks (PubMed: 17308053). Through these activities, it regulates protein synthesis and gene transcription, particularly as a co-regulator of the MYC oncogene and the osteoblast-specific transcription factor Osterix (PubMed: 23103944). RIOX1 is frequently overexpressed in various cancers, such as non-small cell lung cancer and colorectal cancer, where it is associated with increased cell proliferation, metastasis, and poor patient prognosis (PubMed: 27473587). Although no clinical drugs currently target RIOX1, it is considered a promising therapeutic target, and research is ongoing to develop selective small-molecule inhibitors for oncological applications (PubMed: 23103944).

Other names

Nucleolar protein 66NO66MAPJDMyc-associated protein with JmjC domainC14orf169JMJD9hsNO66ROXURLC260S ribosomal protein L8 histidine hydroxylaseBifunctional lysine-specific demethylase and histidyl-hydroxylase NO66

Inhibition of the Fe(II) and 2-oxoglutarate-dependent catalytic activity of the JmjC domain, preventing histone demethylation and ribosomal protein hydroxylation.