Fat mass and obesity-associated protein (FTO) (FTO)

Fat mass and obesity-associated protein (FTO) is a nuclear-localized enzyme belonging to the AlkB family of alpha-ketoglutarate-dependent dioxygenases (UniProt: Q9C0B1). Its primary biological role is as a demethylase for N6-methyladenosine (m6A) in RNA, making it a key 'eraser' in the epitranscriptomic landscape (Science, 2007; 318:1469-1472). FTO plays a pivotal role in regulating energy metabolism, adipocyte differentiation, and appetite through its effects on the stability and processing of mRNA transcripts involved in metabolic pathways (Nature, 2014; 507:371-375). Genetic variants within the FTO gene are strongly associated with increased fat mass, higher body weight, and risk for type 2 diabetes. In recent years, FTO has also been identified as a significant target in oncology, particularly in acute myeloid leukemia (AML) and various solid tumors, where its overexpression promotes oncogenic signaling by reducing m6A levels on tumor-promoting mRNAs (Cancer Cell, 2017; 31:127-141). Therapeutic strategies involving FTO often utilize small-molecule inhibitors to restore m6A levels, thereby suppressing tumor growth or modulating metabolic dysfunction (Frontiers in Genetics, 2020; 11:567).

Other names

Alpha-ketoglutarate-dependent dioxygenase FTOGDF72ALKBH9Fat mass and obesity associated proteinFat mass and obesity-associated gene

Competitive inhibition of the alpha-ketoglutarate-dependent oxidative demethylase activity, leading to increased levels of N6-methyladenosine (m6A) on target mRNA transcripts, which subsequently alters gene expression, mRNA stability, and protein translation (Cancer Cell, 2019; 35:677-689).