Alpha-ketoglutarate-dependent dioxygenase ALKBH3 (ALKBH3)

Alpha-ketoglutarate-dependent dioxygenase ALKBH3 (ALKBH3) is an iron- and alpha-ketoglutarate-dependent dioxygenase that functions as a demethylase for both DNA and RNA. It specifically removes methyl groups from 1-methyladenosine (m^1A) and 3-methylcytosine (m^3C) in tRNA and single-stranded DNA, helping to repair alkylation damage and regulate epitranscriptomic marks. ALKBH3 is preferentially expressed in various cancers—where it promotes cell proliferation, migration, invasion, and protein synthesis partly by generating tRNA-derived small RNAs after tRNA demethylation. Mechanistically, ALKBH3 supports ribosome assembly and helps cancer cells prevent apoptosis. It also regulates the ciliary cycle by controlling the m^1A modification status of Aurora A kinase mRNA. Therapeutically, ALKBH3 represents an emerging target for novel anticancer strategies, with research focused on small molecule inhibitors and potential biomarker applications for aggressive tumor identification

Other names

AlkB homolog 3AlkB family member 3ABH3Alpha-ketoglutarate-dependent dioxygenase ALKBH3

Inhibition of ALKBH3 leads to increased methylation of DNA/RNA, impairs DNA/RNA repair, decreases synthesis of proteins crucial for cancer cell survival and proliferation, and may sensitize cells to chemotherapeutics