Practice question

Beta-catenin degradation circuit includes scaffold proteins regulating turnover tightly and rapidly. In absence of Wnt, cytosolic destruction complex assembles Axin dimer, APC tumor suppressor, CK1alpha, GSK3beta. CK1alpha primes Ser45 phosphorylation, then Glycogen synthase kinase 3 phosphorylates Ser33, Ser37, Thr41 creating phosphodegron recognized by beta-TrCP SCF E3 ubiquitin ligase leading to polyubiquitination and proteasomal degradation in proteasome. Protein kinase A phosphorylates other sites increasing activity, JAK and MAP kinase not primary degradative kinases. This constitutive turnover keeps nuclear beta-catenin low ensuring target genes off until Wnt inhibits complex via Dishevelled LRP6 phosphorylation.