Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes.
Histone deacetylases (HDACs) are thought to function as critical mediators of transcriptional repression. However, the physiological targets and posttranslational modifications of the class II HDACs are largely unknown. Here we show that the C terminus of HDAC 6 is both necessary and sufficient for specific association with polyubiquitin. This region contains a putative zinc finger but lacks significant similarity to other known ubiquitin binding domains. Thus, we have designated this region as a PAZ domain, for Polyubiquitin Associated Zinc finger. Although the PAZ domain possesses homology with the zinc finger of deubiquitinating enzymes, it is dispensable for the deubiquitinating activity we find associated with HDAC6 following immunopurification. We also show that both HDAC 5 and HDAC 6 are ubiquitinated in vitro and in vivo. However, both of these proteins are stable in vivo and do not appear to be targeted for rapid degradation by the proteasome. Thus, HDAC6 is linked to the ubiquitin system via ubiquitin conjugation, polyubiquitin binding, and copurification with deubiquitinating enzymes.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D010450:Endopeptidases / Q000302:isolation & purification; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D025821:Polyubiquitin / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D011994:Recombinant Proteins; D025821:Polyubiquitin; D010450:Endopeptidases; C404500:HDAC5 protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases