Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways.
The immunopurification of the endogenous cytoplasmic murine histone deacetylase 6 (mHDAC6), a member of the class II HDACs, from mouse testis cytosolic extracts allowed the identification of two associated proteins. Both were mammalian homologues of yeast proteins known to interact with each other and involved in the ubiquitin signaling pathway: p97/VCP/Cdc48p, a homologue of yeast Cdc48p, and phospholipase A2-activating protein, a homologue of yeast UFD3 (ubiquitin fusion degradation protein 3). Moreover, in the C-terminal region of mHDAC6, a conserved zinc finger-containing domain named ZnF-UBP, also present in several ubiquitin-specific proteases, was discovered and was shown to mediate the specific binding of ubiquitin by mHDAC6. By using a ubiquitin pull-down approach, nine major ubiquitin-binding proteins were identified in mouse testis cytosolic extracts, and mHDAC6 was found to be one of them. All of these findings strongly suggest that mHDAC6 could be involved in the control of protein ubiquitination. The investigation of biochemical properties of the mHDAC6 complex in vitro further supported this hypothesis and clearly established a link between protein acetylation and protein ubiquitination.
Seigneurin-Berny
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Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, Equipe Chromatine et Expression des Gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France.
Verdel
A
A
Curtet
S
S
Lemercier
C
C
Garin
J
J
Rousseaux
S
S
Khochbin
S
S
D000107:Acetylation; D000251:Adenosine Triphosphatases; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D064570:Ubiquitin-Specific Proteases; D014452:Ubiquitins / Q000378:metabolism*; D000074405:Valosin Containing Protein; D016335:Zinc Fingers / Q000502:physiology
D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D011506:Proteins; D014452:Ubiquitins; C055324:phospholipase A2-activating protein; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases; C433811:HDAC6 protein, human; 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