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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
HDAC6-p97/VCP controlled polyubiquitin chain turnover
Cyril Boyault1, Benoit Gilquin, Yu Zhang
1INSERM U309, Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, Equipe chromatine et expression des gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, La Tronche, France.
The EMBO Journal
|July 1, 2006
Summary
Histone deacetylase 6 (HDAC6) binds ubiquitin via its ZnF-UBP domain, controlling protein aggregate formation. The chaperone p97/VCP counteracts HDAC6, promoting protein degradation and ubiquitin turnover.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- HDAC6 is a unique cytoplasmic deacetylase.
- HDAC6 interacts with ubiquitin.
- Cellular polyubiquitin chain turnover is critical for protein homeostasis.
Purpose of the Study:
- To characterize the ubiquitin-binding domain of HDAC6 (ZnF-UBP).
- To investigate the biological functions of HDAC6-ubiquitin interactions.
- To elucidate the roles of HDAC6 and p97/VCP in protein fate determination.
Main Methods:
- Biophysical techniques
- Biochemical assays
- Biological approaches
Main Results:
- The HDAC6 ZnF-UBP domain exhibits high affinity for ubiquitin monomers.
- HDAC6 negatively controls cellular polyubiquitin chain turnover.
- p97/VCP dissociates HDAC6-ubiquitin complexes, counteracting HDAC6's pro-aggregation effects.
Conclusions:
- A balance between HDAC6 and p97/VCP dictates the fate of ubiquitinated misfolded proteins.
- p97/VCP promotes protein degradation and ubiquitin turnover.
- HDAC6 favors the accumulation of ubiquitinated protein aggregates and inclusion bodies.
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