FRAT regulator of Wnt signaling pathway 1 (FRAT1)

FRAT regulator of Wnt signaling pathway 1 (FRAT1) is a GSK-3-binding oncoprotein that positively regulates the canonical Wnt/β-catenin signaling pathway by inhibiting glycogen synthase kinase-3 (GSK-3)-mediated phosphorylation of β-catenin, thereby stabilizing β-catenin and promoting downstream transcriptional activation. FRAT1 is implicated in processes such as tumor progression and lymphomagenesis, particularly in advanced T-cell lymphomas and certain other cancers (ovarian, lung, prostate). It also exhibits a role at the intersection of canonical and noncanonical Wnt pathways, potentially contributing to signaling cascades such as JNK/AP-1 activation and tissue polarity. While originally considered essential for canonical Wnt signaling, knockout mouse studies indicate that FRAT1 is not strictly required for baseline Wnt activity, suggesting its physiological role may be context-dependent or redundant. No approved drugs are known to specifically target FRAT1, but its function as an oncoprotein and regulator of a critical cancer-related pathway makes it a subject of interest in cancer research and experimental therapeutics.

Other names

Proto-oncogene FRAT1Frequently rearranged in advanced T-cell lymphomas 1FRAT-1GBPFRAT regulator of WNT signaling pathway 1frequently rearranged in advanced T cell lymphomas

Modulation of Wnt/β-catenin signaling by inhibition of GSK-3-mediated β-catenin phosphorylation