CA-FOXO1

CA-FOXO1 (Constitutively Active Forkhead Box Protein O1) is a genetically engineered mutant form of the FOXO1 transcription factor designed to remain in a permanently active state within the cell nucleus. This constitutive activity is typically achieved by mutating three conserved Akt phosphorylation sites (Thr24, Ser256, and Ser319 in humans) to alanine, which prevents Akt-mediated phosphorylation, nuclear export, and subsequent cytoplasmic degradation. In research settings, particularly those investigating metabolic diseases and skeletal muscle physiology, CA-FOXO1 is used as a tool to model the pathological effects of chronic FOXO1 activation, such as that seen in insulin-deficient diabetes. Studies demonstrate that CA-FOXO1 expression in skeletal muscle leads to the downregulation of mitochondrial oxidative phosphorylation (OXPHOS) genes (e.g., Ndufv2, Sdhb) and the induction of atrophy-related genes (e.g., MuRF1, Gadd45a), resulting in impaired mitochondrial respiration and reduced muscle strength prior to measurable loss of muscle mass.

Other names

constitutively active FOXO1constitutively active Forkhead box protein O1