biostudies-literatureKlement KDeutsche ForschungsgemeinschaftWilhelm Sander-StiftungFriedrich-Alexander-Universität Erlangen-NürnbergIZKFjcs261214https://www.ebi.ac.uk/biostudies/studies/S-EPMC10652037biostudies-literatureUnknown136(20)Axin (also known as AXIN1) is a central negative regulator of the proto-oncogenic Wnt/β-catenin signaling pathway, as axin condensates provide a scaffold for the assembly of a multiprotein complex degrading β-catenin. Axin, in turn, is degraded through tankyrase. Consequently, tankyrase small-molecule inhibitors block Wnt signaling by stabilizing axin, revealing potential for cancer therapy. Here, we discovered that axin is phosphorylated by casein kinase 1 alpha 1 (CSNK1A1, also known as CK1α) at an N-terminal casein kinase 1 consensus motif, and that this phosphorylation is antagonized by the catalytic subunit alpha of protein phosphatase 1 (PPP1CA, hereafter referred to as PP1). Axin condensates promoted phosphorylation by enriching CK1α over PP1. Importantly, the phosphorylation took pJournal of cell sciencePhosphorylation of axin within biomolecular condensates counteracts its tankyrase-mediated degradation.PMC10652037D30BE 7055/2-12018.017.2Bruckner MKlement KBernkopf DBfalsePhosphorylation of axin within biomolecular condensates counteracts its tankyrase-mediated degradation.Axin (also known as AXIN1) is a central negative regulator of the proto-oncogenic Wnt/β-catenin signaling pathway, as axin condensates provide a scaffold for the assembly of a multiprotein complex degrading β-catenin. Axin, in turn, is degraded through tankyrase. Consequently, tankyrase small-molecule inhibitors block Wnt signaling by stabilizing axin, revealing potential for cancer therapy. Here, we discovered that axin is phosphorylated by casein kinase 1 alpha 1 (CSNK1A1, also known as CK1α) at an N-terminal casein kinase 1 consensus motif, and that this phosphorylation is antagonized by the catalytic subunit alpha of protein phosphatase 1 (PPP1CA, hereafter referred to as PP1). Axin condensates promoted phosphorylation by enriching CK1α over PP1. Importantly, the phosphorylation took p2023-01-01T00:00:00Z2023 Oct2026-05-29T10:23:42.779Z2025-04-04T11:02:33.729ZS-EPMC106520373772109310.1242/jcs.261214