Glucose Deprivation Triggers Protein Kinase C-dependent β-Catenin Proteasomal Degradation

Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of beta-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G(1) transition and enhancement of the LC3-II protein levels, whereas beta-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3 beta was unable to abolish the glucose deprivation-mediated beta-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3 beta-independent protein degradation. Intriguingly, the inhibition of PKC beta using a pharmacological inhibitor and transfection of siRNA for PKC alpha was observed to effectively block glucose deprivation- induced beta-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G(1) population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3 beta-independent protein degradation of beta-catenin, leading to autophagy.