Figure 5. A model for quality control autophagy and nonselective autophagy in Huntington disease. The model proposes that EP300-CREBBP regulates the switch between QC autophagy and autophagic cell death in neuronal cells. In early stages, QC autophagy mediates the remobilization and degradation of HTT-containing protein aggregates. The activity of EP300-CREBBP is enhanced by CHUK. Acetylation by CREBBP facilitates the export of mutant intranuclear HTT proteins and promotes autophagy-mediated clearance (aggrephagy). This clearance is likely promoted by interaction with SQSTM1. In advanced stages of Huntington disease (late stage), the mutant HTT protein-containing inclusion bodies accumulate in the nucleus. This results in EP300-CREBBP sequestration and inhibition, and ultimately leads to intensified autophagy or autophagic cell death.