GSK-3-binding protein FRAT2 (FRAT2)

GSK-3-binding protein FRAT2 (FRAT2) is a small (233 amino acid) protein encoded by an intronless gene located on chromosome 10q24.1 in humans[1][4][5][10]. It belongs to the GSK-3-binding protein family and acts as a positive regulator of the canonical Wnt signaling pathway by binding to glycogen synthase kinase 3 beta (GSK-3β), thereby preventing phosphorylation and degradation of beta-catenin[1][4]. This stabilization of beta-catenin leads to activation of transcriptional programs controlling cell proliferation and survival. FRAT2 is expressed at higher levels in certain tumor types (such as basal-like breast cancer, stomach cancer, T-cell lymphoma, and some leukemias), where its upregulation may contribute to cancer progression through heightened Wnt signaling activity[1][2][4][5]. While drugs targeting the Wnt pathway exist, there are no known clinically used drugs that specifically inhibit or modulate FRAT2, but it has been suggested as a target for new anticancer therapies given its role in tumor biology and lack of existing specific inhibitors[2][7][10].

Other names

FRAT regulator of Wnt signaling pathway 2Frequently rearranged in advanced T-cell lymphomas 2FRAT-2GSK-3-binding protein FRAT2WNT signaling pathway regulator

Inhibition of GSK-3 (by competitive scaffolding/binding, which leads to beta-catenin stabilization and activation of Wnt signaling)[1][2][7]