title: HDAC6-p97/VCP controlled polyubiquitin chain turnover.
abstract: HDAC6 is a unique cytoplasmic deacetylase capable of interacting with ubiquitin. Using a combination of biophysical, biochemical and biological approaches, we have characterized the ubiquitin-binding domain of HDAC6, named ZnF-UBP, and investigated its biological functions. These studies show that the three Zn ion-containing HDAC6 ZnF-UBP domain presents the highest known affinity for ubiquitin monomers and mediates the ability of HDAC6 to negatively control the cellular polyubiquitin chain turnover. We further show that HDAC6-interacting chaperone, p97/VCP, dissociates the HDAC6-ubiquitin complexes and counteracts the ability of HDAC6 to promote the accumulation of polyubiquitinated proteins. We propose that a finely tuned balance of HDAC6 and p97/VCP concentrations determines the fate of ubiquitinated misfolded proteins: p97/VCP would promote protein degradation and ubiquitin turnover, whereas HDAC6 would favour the accumulation of ubiquitinated protein aggregates and inclusion body formation.
authors.affiliation: INSERM 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.
authors.forename: Cyril
authors.initials: C
authors.lastname: Boyault
authors.forename: Benoit
authors.initials: B
authors.lastname: Gilquin
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rybin
authors.forename: Elspeth
authors.initials: E
authors.lastname: Garman
authors.forename: Wolfram
authors.initials: W
authors.lastname: Meyer-Klaucke
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Müller
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D016475:3T3 Cells; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000502:physiology*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D025821:Polyubiquitin / Q000378:metabolism*; D017510:Protein Folding; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D025821:Polyubiquitin; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse