ALKBH5, RNA demethylase ALKBH5, ALKB homolog 5 (44 kDa) is a dioxygenase enzyme which demethylates RNA in a reaction requiring oxygen, alpha-ketoglutarate, and iron. ALKBH5 and fat mass and obesity-associated protein (FTO) are involved in the demethylation of N6-methyladenosine or m6A mRNA, the most common post-translational modification in eukaryotic mRNA. m6A mRNA modifications are very dynamic; they are introduced into the mRNA by m6A methyltransferases (e.g., METTL3/14 and KIAA1429), removed by erasers such as FTO and ALKBH5, and decoded by m6A binding proteins (e.g., IGF2BP1 and YTHDF1/2/3). m6A mRNA modifications play roles in regulating mRNA splicing, processing, translation and stability. m6A mRNA modifications are also associated with pathological states including cancer (1, 2).
ALKBH5 has been implicated in various physiological and pathophysiological processes. In mice, ALKBH5 is highly expressed in the testes where loss of ALKBH5 expression leads to decreased spermatogenesis, abnormal spermatozoa and increased apoptosis (3). In glioblastoma, ALKBH5 overexpression promotes stemness and tumor progression (2). In breast cancer cells under hypoxic conditions, HIF-1 alpha and HIF-2 alpha induce the expression of ALKH5 and leads to increased demethylation and expression of Nanog thus promoting breast cancer stem cell properties (4).
1. Chen, X. Y., Zhang, J., & Zhu, J. S. (2019). The role of m6A RNA methylation in human cancer. Molecular Cancer. https://doi.org/10.1186/s12943-019-1033-z
2. Deng, X., Su, R., Weng, H., Huang, H., Li, Z., & Chen, J. (2018). RNA N 6 -methyladenosine modification in cancers: Current status and perspectives. Cell Research. https://doi.org/10.1038/s41422-018-0034-6
3. Meyer, K. D., & Jaffrey, S. R. (2014). The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/nrm3785
4. Zhang, C., Samanta, D., Lu, H., Bullen, J. W., Zhang, H., Chen, I.,... Semenza, G. L. (2016). Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1602883113
|Product By Gene ID
- Alkylated DNA repair protein alkB homolog 5
- EC 1.14.11.-
- oxoglutarate and iron-dependent oxygenase domain containing
- probable alpha-ketoglutarate-dependent dioxygenase ABH5
- alkB, alkylation repair homolog 5 (E. coli)