Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes

Abstract

Histone deacetylase (HDAC) 6 is the best-characterized class IIb deacetylase that regulates many important biological processes via the formation of complexes with its partner proteins. HDAC6 is important both for cytoplasmic and nuclear functions. Unlike other deacetylases, HDAC6 has unique substrate specificity for nonhistone proteins. Such diverse functions of HDAC6 suggest that it serves a potential therapeutic target for the treatment of a wide range of diseases. This therapeutic interest in HDAC6 stems from the observation that HDAC6 may be overexpressed or deregulated in various cancers, neurodegenerative diseases and inflammatory disorders. Despite extensive efforts, however, very few HDAC6-selective inhibitors have been identified and the precise structural determinants remain undefined. Future efforts aiming to better define the structure and function of HDAC6 should provide the basis for the discovery of novel effective inhibitors. In this review, we focus on recent studies that highlight the importance of HDAC6-mediated biological processes, disease mechanisms and HDAC6-selective inhibitors.

High-resolution mapping of H4K16 and H3K23 acetylation reveals conserved and unique distribution patterns inArabidopsisand rice

“…[14][15][16][17][18] Besides its role in gene expression, plant histone acetylation plays crucial roles in the crosstalk between genomes and the environment during plant responses to diverse stresses at the cellular and organismal levels. [19][20][21][22][23][24] Acetylation occurs at many histone lysine residues and regulates chromatin activity by at least 2 different mechanisms. On the one hand, individual acetylation marks have precise function on a specific chromatin-based process independent of other acetylated residues.…”

Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy

“…Unlike other HDACs, HDAC6 is predominantly cytoplasmic and affects cytoskeletal dynamics through deacetylation of α-tubulin and cortactin (34). Acetylated tubulin can affect the stability of microtubules, and recent data suggest that acetylated tubulin may augment assembly of autophagic cargo along microtubules, thereby priming the cell for increased autophagic degradation (21).…”

Cellular defence or viral assist: the dilemma of HDAC6

“…Indeed, HDAC6 regulates many important biological processes, including cell migration, immune response, cell proliferation and differentiation, and the degradation of misfolded proteins through both deacetylase-and ubiquitin-dependent mechanisms (Fig. 1) [5,7].…”

“…HDAC6-dependent Hsp90 deacetylation may affect the instability of some of its client proteins with critical roles in cell growth and survival [27]. Furthermore, proteomic identification and functional characterization of other substrates, such as b-catenin, Hsc70 and survivin, may provide clues about the role of HDAC6 in the mechanisms of pathology and physiology [7,28].…”

“…HDAC6, in particular, has distinct structure features and unique cytoplasmic functions in the regulation of cytoskeleton, cell migration, cell reprogramming and pluripotency [4,5]. Upregulation or activation of HDAC6 has also been implicated in tumorigenesis, neurodegenerative diseases and inflammatory disorders [6,7], implying HDAC6 is a potential therapeutic target for pharmacological intervention strategy. While the list of cytoplasmic acetylated proteins controlled by HDAC6 is rapidly growing, the function of HDAC6 in viral infection is still poorly understood.…”