Autophagy, ubiquitin and polyglutamine diseases 

Nature  545, 108–111 

Expanded polyglutamine (polyQ) tracts in different proteins are a common feature of many neurodegenerative diseases. Many normal proteins also carry these tracts, although their function remains unclear. We show that polyQ tracts in a normal ataxin protein have a role in the degradative process of autophagy. In this case, the polyQ domain allows ataxin 3 interaction with the autophagy mediator beclin 1. Ataxin 3 can thus deubiquitinate beclin 1, preventing its degradation by the proteasome and allowing it to initiate autophagy. We not only demonstrate the relevance of our findings to the process of autophagy in neurons, but also show how, under disease conditions, the polyQ tracts in mutant proteins compete with those in ataxin 3 to prevent beclin 1 stabilization and so impair starvation-induced autophagy.