Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has a unique structure with two catalytic domains and a domain binding ubiquitin with high affinity. This enzyme was recently identified as a multisubstrate protein deacetylase that can act on acetylated histone tails, alpha-tubulin and Hsp90. To investigate the in vivo functions of HDAC6 and the relevance of tubulin acetylation/deacetylation, we targeted the HDAC6 gene by homologous recombination in embryonic stem cells and generated knockout mice. HDAC6-deficient mice are viable and fertile and show hyperacetylated tubulin in most tissues. The highest level of expression of HDAC6 is seen in the testis, yet development and function of this organ are normal in the absence of HDAC6. Likewise, lymphoid development is normal, but the immune response is moderately affected. Furthermore, the lack of HDAC6 results in a small increase in cancellous bone mineral density, indicating that this deacetylase plays a minor role in bone biology. HDAC6-deficient mouse embryonic fibroblasts show apparently normal microtubule organization and stability and also show increased Hsp90 acetylation correlating with impaired Hsp90 function. Collectively, these data demonstrate that mice survive well without HDAC6 and that tubulin hyperacetylation is not detrimental to normal mammalian development.

Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally

HDAC6 : a key regulator of cytoskeleton, cell migration and cell-cell interactions

https://cyberleninka.org/article/n/1310744.pdf

Poly(amidoamine), polypropylenimine, and related dendrimers and dendrons possessing different 1 → 2 branching motifs : An overview of the divergent procedures

Histone deacetylase 6 (HDAC6) is a unique enzyme with specific structural and functional features. It is actively or stably maintained in the cytoplasm and is the only member, within the histone deacetylase family, that harbors a full duplication of its deacetylase homology region followed by a specific ubiquitin-binding domain at the C-terminus end. Accordingly, this deacetylase functions at the heart of a cellular regulatory mechanism capable of coordinating various cellular functions largely relying on the microtubule network. Moreover, HDAC6 action as a regulator of the HSP90 chaperone activity adds to the multifunctionality of the protein, and allows us to propose a critical role for HDAC6 in mediating and coordinating various cellular events in response to different stressful stimuli.

HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination.

A review of nanocarriers for the delivery of small interfering RNA

Efficient human immunodeficiency virus (HIV)-1 infection depends on multiple interactions between the viral gp41/gp120 envelope (Env) proteins and cell surface receptors. However, cytoskeleton-associated proteins that modify membrane dynamics may also regulate the formation of the HIV-mediated fusion pore and hence viral infection. Because the effects of HDAC6-tubulin deacetylase on cortical α-tubulin regulate cell migration and immune synapse organization, we explored the possible role of HDAC6 in HIV-1-envelope-mediated cell fusion and infection. The binding of the gp120 protein to CD4+-permissive cells increased the level of acetylated α-tubulin in a CD4-dependent manner. Furthermore, overexpression of active HDAC6 inhibited the acetylation of α-tubulin, and remarkably, prevented HIV-1 envelope-dependent cell fusion and infection without affecting the expression and codistribution of HIV-1 receptors. In contrast, knockdown of HDAC6 expression or inhibition of its tubulin deacetylase activity strongly enhanced HIV-1 infection and syncytia formation. These results demonstrate that HDAC6 plays a significant role in regulating HIV-1 infection and Env-mediated syncytia formation.

/pdf/histone-deacetylase-6-regulates-human-immunodeficiency-virus-37ybeaqwkk.pdf

Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection

A synthetic strategy has been developed for the preparation of new peripheral amine- or ammonium-terminated carbosilane dendrimers of type nG-[Si(OCH2CH2NMe2)y]x or nG-[Si(OCH2CH2NMe3+I–)y]x, respectively. It consists of the alcoholysis of well-known chlorosilane-terminated dendrimers with N,N-dimethylethanolamine and the subsequent quaternization with MeI. All these systems are susceptible to hydrolysis, although the decomposition depends on concentration and dendrimer generation. Evaluation of dendrimer toxicities by phase-contrast light microscopy and MTT assay were carried out, and evidence of dendrimer/oligonucleotide complex formation was carried out by gel electrophoresis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Novel Water-Soluble Carbosilane Dendrimers: Synthesis and Biocompatibility

Prevalence and factors involved in discordant responses to highly active antiretroviral treatment in a closely followed cohort of treatment-naïve HIV-infected patients

Gerónimo Fernández

Papers

Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection

Novel Water-Soluble Carbosilane Dendrimers: Synthesis and Biocompatibility

Prevalence and factors involved in discordant responses to highly active antiretroviral treatment in a closely followed cohort of treatment-naïve HIV-infected patients

Control of HIV-1 RNA load after HAART interruption: relationship with CCR5 co-receptor density and proviral DNA load in HIV-infected patients.