Polyglutamine tracts regulate autophagy

Avraham Ashkenazi, Carla F. Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C. Hardenberg, Sara Imarisio, Fiona M. Menzies, David C. Rubinsztein

Research output: Contribution to journalComment/debatepeer-review


Expansions of polyglutamine (polyQ) tracts in different proteins cause 9 neurodegenerative conditions, such as Huntington disease and various ataxias. However, many normal mammalian proteins contain shorter polyQ tracts. As these are frequently conserved in multiple species, it is likely that some of these polyQ tracts have important but unknown biological functions. Here we review our recent study showing that the polyQ domain of the deubiquitinase ATXN3/ataxin-3 enables its interaction with BECN1/beclin 1, a key macroautophagy/autophagy initiator. ATXN3 regulates autophagy by deubiquitinating BECN1 and protecting it from proteasomal degradation. Interestingly, expanded polyQ tracts in other polyglutamine disease proteins compete with the shorter ATXN3 polyQ stretch and interfere with the ATXN3-BECN1 interaction. This competition results in decreased BECN1 levels and impaired starvation-induced autophagy, which phenocopies the loss of autophagic function mediated by ATXN3. Our findings describe a new autophagy-protective mechanism that may be altered in multiple neurodegenerative diseases.

Original languageEnglish
Pages (from-to)1613-1614
Number of pages2
Issue number9
Publication statusPublished - Sep 2 2017


  • ataxin-3
  • autophagy
  • Beclin 1
  • Huntington's disease
  • polyglutamine
  • spinocerebellar ataxia

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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