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Related Experiment Video

Updated: Feb 26, 2026

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

Polyglutamine tracts regulate autophagy.

Avraham Ashkenazi¹, Carla F Bento¹, Thomas Ricketts¹

¹a Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR) , University of Cambridge , Cambridge , UK.

|July 20, 2017

Summary

This summary is machine-generated.

Short polyglutamine (polyQ) tracts in ataxin-3 protein protect autophagy by interacting with beclin 1. Expanded polyQ tracts disrupt this interaction, impairing autophagy and potentially contributing to neurodegenerative diseases.

Keywords:

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

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Assays for the Degradation of Misfolded Proteins in Cells

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Published on: August 28, 2016

Area of Science:

Neurobiology
Molecular Biology
Cellular Biology

Background:

Polyglutamine (polyQ) tract expansions in proteins are linked to nine neurodegenerative diseases.
Shorter, conserved polyQ tracts in normal mammalian proteins suggest important biological functions.
The deubiquitinase ATXN3/ataxin-3 contains a polyQ domain with a potentially crucial role.

Purpose of the Study:

To investigate the function of the ATXN3 polyQ domain in protein interactions and cellular processes.
To elucidate the mechanism by which ATXN3 regulates autophagy.
To explore how expanded polyQ tracts in other proteins might interfere with normal ATXN3 function.

Main Methods:

Studied the interaction between the ATXN3 polyQ domain and BECN1/beclin 1.
Investigated ATXN3's role in deubiquitinating BECN1 and its effect on proteasomal degradation.
Examined the impact of expanded polyQ tracts on the ATXN3-BECN1 interaction and subsequent autophagy.

Main Results:

The ATXN3 polyQ domain facilitates interaction with BECN1, a key autophagy initiator.
ATXN3 regulates autophagy by deubiquitinating BECN1, preventing its proteasomal degradation.
Expanded polyQ tracts from other disease proteins compete with ATXN3's polyQ stretch, disrupting the ATXN3-BECN1 interaction.
This disruption leads to reduced BECN1 levels and impaired starvation-induced autophagy.

Conclusions:

A novel autophagy-protective mechanism involving the ATXN3 polyQ domain and BECN1 interaction has been identified.
Impairment of this mechanism by expanded polyQ tracts may contribute to neurodegenerative conditions.
This finding offers new insights into the pathogenesis of polyglutamine diseases and suggests potential therapeutic targets.