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BAG6 regulates the quality control of a polytopic ERAD substrate
Aishwarya Payapilly1, Stephen High2
1Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Journal of Cell Science
|May 9, 2014
Summary
BAG6 protein quality control is complex; while knockdown reduces protein degradation, overexpression paradoxically delays it by inhibiting the BAG6 complex, impacting ubiquitin homeostasis.
Area of Science:
- Molecular Biology
- Cellular Biology
- Protein Degradation
Background:
- BAG6 is involved in protein quality control.
- Endoplasmic-reticulum-associated degradation (ERAD) removes misfolded proteins from the ER.
- The polytopic membrane protein OpD is used as a model substrate.
Purpose of the Study:
- To investigate the role of BAG6 in ERAD.
- To elucidate the distinct mechanisms of BAG6 knockdown and overexpression on OpD degradation.
Main Methods:
- BAG6 knockdown and overexpression experiments.
- Analysis of OpD polyubiquitylation levels.
- Assessment of BAG6 domain function in OpD stabilization.
Main Results:
- Both BAG6 knockdown and overexpression delay OpD degradation via distinct mechanisms.
- Knockdown reduces OpD polyubiquitylation; overexpression increases it.
- Exogenous BAG6 domains are dispensable for OpD stabilization and increased polyubiquitylation.
Conclusions:
- Endogenous BAG6 promotes OpD degradation, but exogenous BAG6 inhibits it, possibly via a dominant-negative effect.
- Cellular BAG6 levels influence overall polyubiquitylation, affecting ubiquitin homeostasis.
- Exogenous BAG6 likely interferes with the proteasomal delivery of OpD.
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