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06:51
Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
Published on: July 21, 2021
Polyglutamined expanded androgen receptor interacts with chaperonin CCT
Suttikarn Pongtepaditep1, Thawornchai Limjindaporn, Patcharee Lertrit
1Division of Molecular Genetics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
European Journal of Medical Genetics
|July 17, 2012
Summary
The chaperonin containing TCP1 (CCT) complex binds to the androgen receptor, particularly the polyglutamine-expanded form. This interaction suggests CCT chaperonin plays a role in managing misfolded polyglutamine proteins, offering therapeutic potential.
Area of Science:
- Molecular biology
- Cell biology
- Protein folding
Background:
- CCT chaperonin is a conserved molecular machine crucial for protein folding in eukaryotes.
- CCT chaperonin interacts with huntingtin, reducing protein aggregation and enhancing cell survival.
- Androgen receptor (AR) dysfunction, often due to polyglutamine expansion, is implicated in diseases.
Purpose of the Study:
- To identify specific CCT chaperonin subunits that interact with the androgen receptor.
- To investigate the binding affinity of CCT chaperonin to wild-type versus polyglutamine-expanded androgen receptor.
- To validate the interaction between CCT chaperonin and androgen receptor in mammalian cells.
Main Methods:
- Yeast-two-hybrid screening to identify interacting proteins.
- Binding assays to compare affinity for wild-type and mutant androgen receptor.
- Mammalian cell culture and co-localization studies using microscopy.
Main Results:
- Subunit 6 of the CCT chaperonin complex was identified as an interactor of the androgen receptor.
- CCT chaperonin exhibited higher binding affinity for polyglutamine-expanded androgen receptor compared to the wild-type.
- Co-localization of CCT chaperonin subunit 6 and androgen receptor was observed in the cytosol of mammalian cells.
Conclusions:
- The androgen receptor, particularly its polyglutamine-expanded form, is a substrate for CCT chaperonin.
- CCT chaperonin plays a significant role in modulating the folding of polyglutamine-expanded proteins.
- CCT chaperonin represents a potential therapeutic target for diseases associated with polyglutamine expansion.
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