Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules

Skultetyova, L.; Ustinova, Kseniya; Kutil, Zsófia; Nováková, Zora; Pavlíček, Jiří; Mikešová, Jana; Trapl, Dalibor; Baranová, Petra; Havlínová, Barbora; Hubálek, Martin; Lánský, Zdeněk; Bařinka, Cyril

doi:10.1038/s41598-017-11739-3

Cited by 66 publications

(91 citation statements)

References 70 publications

(75 reference statements)

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“…On the contrary, other enzymes can remove the acetyl group previously added at α K40. The human histone deacetylase 6 (HDAC6) [193,194] and Sirtuin 2 (SIR2) [195] catalyze these reactions in neurons preferentially. α-Tubulin acetylation is abundant in MTs of mature axons, the same that exhibit abundant detyrosination [180].…”

Section: Post-translational Modifications Of Tubulin (Pmt)mentioning

confidence: 99%

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Muñoz-Lasso

Romá‐Mateo

Pallardó

et al. 2020

Cells

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Recent observations related to the structure of the cytoskeleton in neurons and novel cytoskeletal abnormalities involved in the pathophysiology of some neurological diseases are changing our view on the function of the cytoskeletal proteins in the nervous system. These efforts allow a better understanding of the molecular mechanisms underlying neurological diseases and allow us to see beyond our current knowledge for the development of new treatments. The neuronal cytoskeleton can be described as an organelle formed by the three-dimensional lattice of the three main families of filaments: actin filaments, microtubules, and neurofilaments. This organelle organizes well-defined structures within neurons (cell bodies and axons), which allow their proper development and function through life. Here, we will provide an overview of both the basic and novel concepts related to those cytoskeletal proteins, which are emerging as potential targets in the study of the pathophysiological mechanisms underlying neurological disorders.

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Section: Post-translational Modifications Of Tubulin (Pmt)mentioning

confidence: 99%

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Muñoz-Lasso

Romá‐Mateo

Pallardó

et al. 2020

Cells

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“…Full-length wild-type human HDAC6 (wtHDAC6; residues 1-1215; NP_006035.2, UniProtKB-Q9UBN7) was prepared as previously described (28). Briefly, the expression plasmid encoding wtHDAC6 was constructed by using the gatewaybased cloning protocol (cloning primers are shown in Supplemental Table S2).…”

Section: Preparation Of Full-length Human Hdac6mentioning

confidence: 99%

The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries

et al. 2018

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Histone deacetylase 6 (HDAC6) is a multidomain cytosolic hydrolase acting mostly on nonhistone protein substrates. Investigations of the substrate specificity of HDAC6 are confounded by the presence of 2 catalytically active deacetylase domains (DD1 and DD2). In this study, acetylome peptide microarrays and peptide libraries were used to map the substrate specificity of DD1 and DD2 of human HDAC6. The results show that DD1 is solely responsible for the deacetylation of substrates harboring the acetyllysine at their C terminus, whereas DD2 exclusively deacetylates peptides with an internal acetyllysine residue. Also, statistical analysis of the deacetylation data revealed amino acid preferences at individual positions flanking the acetyllysine, where glycine and arginine residues are favored at positions N‐terminal to the central acetyllysine; negatively charged glutamate is strongly disfavored throughout the sequence. Finally, the deacylation activity of HDAC6 was profiled by using a panel of acyl derivatives of the optimized peptide substrate and showed that HDAC6 acts as a proficient deformylase. Our data thus offer a detailed insight into the substrate preferences of the individual HDAC6 domains at the peptide level, and these findings can in turn help in elucidating the biologic roles of the enzyme and facilitate the development of new domain‐specific inhibitors as research tools or therapeutic agents.—Kutil, Z., Skultetyova, L., Rauh, D., Meleshin, M., Snajdr, I., Novakova, Z., Mikesova, J., Pavlicek, J., Hadzima, M., Baranova, P., Havlinova, B., Majer, P., Schutkowski, M., Barinka, C. The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries. FASEB J. 33,4035–4045 (2019). http://www.fasebj.org

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“…The PCR product, following purification and after digestion with SalI-BglII restriction enzymes, was inserted to XhoI and BamHI sites in the pEGFP-C1 vector. The Halotagged HDAC6 construct was a gift from Cyril Barinka (Institute of Biotechnology CAS, Czech Republic) [41].…”

Section: Plasmid Constructsmentioning

confidence: 99%

Interactions between two regulatory proteins of microtubule dynamics, HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8

Oláh¹,

Szunyogh²,

Szénási³

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Degradation of unwanted proteins is important in protein quality control cooperating with the dynein/dynactin-mediated trafficking along the acetylated microtubule (MT) network. Proteins associated directly/indirectly with tubulin/MTs play crucial roles in both physiological and pathological processes. Our studies focus on the interrelationship of the tubulin deacetylase HDAC6, the MT-associated TPPP/p25 with its deacetylase inhibitory potency and the hub dynein light chain DYNLL/LC8, constituent of dynein and numerous other protein complexes. In this paper, evidence is provided for the direct interaction of DYNLL/LC8 with TPPP/p25 and HDAC6 and their assembly into binary/ternary complexes with functional potency. The in vitro binding data was obtained with recombinant proteins and used for mathematical modelling. These data and *REVISED Manuscript (text UNmarked) Click here to view linked References

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Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules

Cited by 66 publications

References 70 publications

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries

Interactions between two regulatory proteins of microtubule dynamics, HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8

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