5b8d

Structural highlights

Function

HDAC6_HUMAN Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin.^{[1] [2]} In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.^{[3] [4]}

See Also

• Histone deacetylase 3D structures

References

1. ↑ Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP. HDAC6 is a microtubule-associated deacetylase. Nature. 2002 May 23;417(6887):455-8. PMID:12024216 doi:http://dx.doi.org/10.1038/417455a
2. ↑ Olzmann JA, Li L, Chudaev MV, Chen J, Perez FA, Palmiter RD, Chin LS. Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J Cell Biol. 2007 Sep 10;178(6):1025-38. PMID:17846173 doi:10.1083/jcb.200611128
3. ↑ Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP. HDAC6 is a microtubule-associated deacetylase. Nature. 2002 May 23;417(6887):455-8. PMID:12024216 doi:http://dx.doi.org/10.1038/417455a
4. ↑ Olzmann JA, Li L, Chudaev MV, Chen J, Perez FA, Palmiter RD, Chin LS. Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J Cell Biol. 2007 Sep 10;178(6):1025-38. PMID:17846173 doi:10.1083/jcb.200611128
5. ↑ Harding RJ, Ferreira de Freitas R, Collins P, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH. Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin. J Med Chem. 2017 Nov 9;60(21):9090-9096. doi: 10.1021/acs.jmedchem.7b00933. Epub , 2017 Oct 27. PMID:29019676 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00933