CDK4-CDK6 inhibitors induce autophagy-mediated degradation of DNMT1 and facilitate the senescence antitumor response

Figures & data

Figure 1. CDK4-CDK6 protect DNMT1 from autophagy. The effect of CDK4-CDK6 on DNMT1 levels can be inhibited by palbociclib or the autophagy inhibitor bafilomycin A₁. The model predicts that a phosphatase can also target DNMT1 for autophagy and that an autophagy receptor able to link DNMT1 to the phagophore (the autophagosome precursor) would be involved. Inhibition of CDK4-CDK6 and targeting of DNMT1 for autophagy allow changes in epigenetic marks, which facilitate the induction of the senescence program in tumor cells. The senescence program itself involves an increase in the autophagy pathway generating a potential positive feedback mechanism to reinforce senescence.