HDAC6 is a microtubule-associated deacetylase

  title={HDAC6 is a microtubule-associated deacetylase},
  author={Charlotte C. Hubbert and Amaris R. Guardiola and Rong‐guang Shao and Yoshiharu Kawaguchi and Akihiro Ito and Andrew Nixon and Minoru Yoshida and Xiao-Fan Wang and Tso-pang Yao},
Reversible acetylation of α-tubulin has been implicated in regulating microtubule stability and function. The distribution of acetylated α-tubulin is tightly controlled and stereotypic. Acetylated α-tubulin is most abundant in stable microtubules but is absent from dynamic cellular structures such as neuronal growth cones and the leading edges of fibroblasts. However, the enzymes responsible for regulating tubulin acetylation and deacetylation are not known. Here we report that a member of the… 

Inhibition of HDAC6 Deacetylase Activity Increases Its Binding with Microtubules and Suppresses Microtubule Dynamic Instability in MCF-7 Cells*

The evidence presented in this study indicated that the increased binding of HDAC6, rather than the acetylation per se, causes microtubule stability, in support of a hypothesis that in addition to its deacetylase function,HDAC6 might function as a MAP that regulates microtubules dynamics under certain conditions.

HDAC‐6 interacts with and deacetylates tubulin and microtubules in vivo

The data provide evidence that HDAC‐6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non‐histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.

Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6

The physical presence of HDAC6 with impaired catalytic activity, rather than tubulin acetylation per se, is the factor responsible for the alteration of microtubule growth velocity inHDAC6 inhibitor-treated cells.

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

Human histone deacetylase 6 (HDAC6) is the major deacetylase responsible for removing the acetyl group from Lys40 of α-tubulin (αK40), which is located lumenally in polymerized microtubules. Here, we

Tubulin Acetyltransferase αTAT1 Destabilizes Microtubules Independently of Its Acetylation Activity

It is demonstrated that αTAT1 has cellular functions that extend beyond its classical enzymatic activity as an α-tubulin acetyltransferase and also acetylates itself in a regulatory mechanism that is required for effective modification of tubulin.

Acetylated α-tubulin residue K394 regulates microtubule stability to shape the growth of axon terminals

The found that an acetylation-blocking mutation in endogenous α-tubulin, K394R, perturbs the synaptic morphogenesis of motoneurons by reducing microtubule stability and suggests that HDAC6 regulates K394 acetylated during synaptic morphogenic.

Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase

The results suggest that Fry plays a crucial role in promoting the level of MT acetylation in the mitotic spindle by inhibiting the tubulin-deacetylase activity of SIRT2.

deacetylase 3 indirectly modulates tubulin acetylation.

It is found that blocking HDAC3 activity using MI192 modulated tubulin acetylation in the human prostate cancercelllinePC3, and data suggest thatHDAC3 indirectly modulates tubulinacetylation.

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

A scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration is suggested.



Microtubules containing acetylated alpha-tubulin in mammalian cells in culture

The observations confirm that the acetylation of alpha-tubulin is a modification occurring in different microtubule structures and in a variety of eukaryotic cells, and could regulate the presence of microtubules in specific intracellular spaces by selective stabilization.

Molecular Cloning and Characterization of a Novel Histone Deacetylase HDAC10*

The identification of a novel class II histone deacetylase with distinct structure, pharmacology and localization is reported, suggesting that HDAC10 might uniquely play roles both in the nucleus, as a transcriptional modulator, and in the cytoplasm in an unidentified role.

Deacetylation of p53 modulates its effect on cell growth and apoptosis

The results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.

Identification of Components of the Murine Histone Deacetylase 6 Complex: Link between Acetylation and Ubiquitination Signaling Pathways

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.

Three proteins define a class of human histone deacetylases related to yeast Hda1p.

Coimmunoprecipitation experiments indicate that these HDAC proteins are not components of the previously identified HDAC1 and HDAC2 NRD and mSin3A complexes, however, HDAC4 andHDAC5 associate with HDAC3 in vivo, which suggests that the human class II HDAC enzymes may function in cellular processes distinct from those of HDACs.

Acetylation: a regulatory modification to rival phosphorylation?

This review sets out what the authors know about the broader substrate specificity and regulation of acetylases and goes on to compare acetylation with the process of phosphorylation.

p300/CBP‐mediated p53 acetylation is commonly induced by p53‐activating agents and inhibited by MDM2

It is demonstrated that, unlike phosphorylation, p53 invariably undergoes acetylation in cells exposed to a variety of stress‐inducing agents including hypoxia, anti‐metabolites, nuclear export inhibitor and actinomycin D treatment, providing evidence that p300/CBP‐mediated acetylations may be a universal and critical modifi cation for p53 function.

Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms

Seven monoclonal antibodies raised against tubulin from the axonemes of sea urchin sperm flagella recognize an acetylated form of alpha-tubulin present in theAxoneme of a variety of organisms, and may allow us to deduce the role of tubulin acetylation in the structure and function of microtubules in vivo.

Differential localisation of tyrosinated, detyrosinated, and acetylated alpha-tubulins in neurites and growth cones of dorsal root ganglion neurons.

Results would be consistent with axonal transport of tyrosinated alpha-tubulin followed by assembly in the growth cone and subsequent detyrosination and acetylation, and may be necessary for the provision of labile microtubules for growth cone motility and extension.