Effects of the Alternative β-Catenin Degradation Pathway and of Axin Degradation at Low Concentrations of APC

(A) The alternative β-catenin degradation pathway (axin independent) can have profound effects on β-catenin levels at low APC concentrations. Variations of β-catenin and axin resulting from changes in APC concentration were calculated from the standard stimulated state. Relative variations were plotted since variation in the share of alternative degradation (1%, 5%, and 10%) results in changes of the standard stimulated state (all parameters are constant). β-Catenin and axin levels for varying contributions of the alternative degradation pathway are as follows: 1.5%, β-catenin 178 nM, axin 0.00728 nM; 5%, β-catenin 151 nM, axin 0.00679 nM; 10%, β-catenin 125 nM, axin 0.00629 nM.

(B) Inhibition of axin degradation reduces β-catenin concentration after loss of APC. Plotted is the concentration of a potential proteasome inhibitor I (scaled to its inhibition constant, KI) necessary to reduce β-catenin concentration to its original level, depending on the concentration of APC.