Human HDAC6 Active Enzyme
- Known as:
- Human HDAC6 Active Enzyme
- Catalog number:
- x1740e
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Exalpha
- Gene target:
- Human HDAC6 Active Enzyme
Related genes to: Human HDAC6 Active Enzyme
- Gene:
- HDAC6 NIH gene
- Name:
- histone deacetylase 6
- Previous symbol:
- -
- Synonyms:
- KIAA0901, JM21, HD6, FLJ16239, PPP1R90
- Chromosome:
- Xp11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2015-09-11
Related products to: Human HDAC6 Active Enzyme
Related articles to: Human HDAC6 Active Enzyme
- Histone deacetylase 6 is a unique cytoplasmic deacetylase implicated in cellular functions such as microtubule dynamics, protein quality control, ubiquitin-mediated degradation and neurodegenerative disorders. The ZnF UBP (zinc finger ubiquitin binding protein) domain of HDAC6 is known to be directly modulate several cellular processes linked to neurodegeneration such as sequestering polyubiquitinated aggregates and regulating protein aggregate clearance mechanisms in neurons. Microtubule associated protein Tau (MAP Tau) undergoes aggregation in neurodegenerative conditions like Alzheimer's disease (AD) and several other tauopathies. Tau is a natively disordered protein which is functionally regulated by wide array of post-translational modifications (PTMs) as well as by interacting with several proteins. This methodological study aims to understand the molecular interaction between HDAC6 ZnF UBP domain and Tau protein in order to elucidate the role of HDAC6 ZnF UBP domain in Tau aggregation and stability. We employed an integrated biochemical, biophysical and computational workflow to characterize the interaction between HDAC6 ZnF UBP and Tau. NMR spectroscopy, isothermal titration calorimetry and pull-down assay with purified HDAC6 ZnF UBP and Tau proteins demonstrated direct interaction between the two, with interaction associated structural perturbations and favourable binding kinetics as observed in NMR and ITC respectively. Computational analyses further suggest the formation of Tau-HDAC6 ZnF UBP complex and provided underlying molecular interactions involved in the binding of these two proteins. The findings in this study helps to advance the current understanding of regulatory role of HDAC6 specifically in Tau biology and further provides a useful framework for investigating the modulation of aggregation prone proteins via protein-protein interaction in neurodegenerative diseases. - Source: PubMed
Publication date: 2026/07/28
Balmik Abhishek AnkurSonawane Shweta KishorGorantla Nalini VijayChinnathambi Subashchandrabose - Post-translational acetylation of cytoplasmic proteins has emerged as a critical regulatory mechanism in neurological disease. Peroxiredoxin 1 (Prdx1), a key antioxidant enzyme, undergoes reversible lysine acetylation that modulates its enzymatic activity. Histone Deacetylase 6 (HDAC6), a predominantly cytoplasmic deacetylase, has been identified as a regulator of Prdx1 acetylation, linking deacetylase activity to redox homeostasis. Accurate detection of Prdx1 deacetylation requires methodological strategies capable of preserving endogenous acetylation states and selectively enriching acetylated protein fractions. This chapter describes a reproducible workflow for assessing HDAC6-mediated Prdx1 deacetylation in cortical tissue which integrates optimized protein extraction under acetylation-preserving conditions, acetyl-lysine-based co-immunoprecipitation, and immunoblot detection of Prdx1. Parallel assessment of total Prdx1 and established HDAC6 substrates enables normalization and validation of deacetylase activity. Quantitative densitometric analysis provides comparative evaluation of acetylation levels across experimental conditions. This methodology offers a practical and translationally applicable approach for investigating non-histone deacetylation mechanisms and can be adapted to other HDAC6-regulated substrates in neurodegenerative research. - Source: PubMed
Publication date: 2026/06/17
Kumar SonaliShanker Ozasvi RBanerjee JyotirmoyDixit Aparna Banerjee - Neurodegenerative disorders are characterized by progressive synaptic failure, neuronal loss, and the accumulation of pathological protein aggregates. A critical but often overlooked driver of this decline is cytoskeletal dysregulation, which compromises essential cellular functions ranging from intracellular transport to morphological stability. Histone Deacetylase 6 (HDAC6) is a central regulator of these dynamics, yet its role in neurodegeneration remains controversial: while its deacetylase activity is often linked to microtubule instability and toxicity, its ubiquitin-binding functions are essential for aggregate clearance. We have previously demonstrated that the ZnF-UBP domain acts as a direct modulator of cytoskeletal architecture, enhancing the formation of actin-rich migratory structures-such as podosomes and lamellipodia-and promoting neuritic outgrowth. It does this by inducing increased localization of actin remodelling proteins to the podosomes, ultimately conferring enhanced migration potential to cells. This chapter highlights the protocols essential for understanding the therapeutic potential of the HDAC6 Zinc Finger Ubiquitin-Binding Protein (ZnF-UBP) domain, in the context of actin remodelling through podosome structures. - Source: PubMed
Publication date: 2026/06/10
Qureshi TazeenBalmik Abhishek AnkurChinnathambi Subashchandrabose - Multiple myeloma (MM) is a malignant blood cancer marked by severe bone destruction and immune microenvironment disruption. Yet relapse and drug resistance remain major clinical challenges. Tanshinone IIA (TIIA) exhibits potent antitumor activity, but its molecular targets and mechanisms in MM remain unclear. Here, we systematically elucidate TIIA's pharmacological mechanisms in MM using network pharmacology, transcriptomics, molecular docking, molecular dynamics (MD) simulations, and in vitro cellular experiments. Histone deacetylase 6 (HDAC6) was identified as a key prognostic target in MM via integrative bioinformatics─combining cross-database analysis, machine learning (LASSO, SVM-RFE, random forest), and survival validation in the MMRF-CoMMpass cohort. Molecular docking and MD simulations showed stable binding of TIIA to HDAC6. In vitro, TIIA directly inhibited HDAC6 enzymatic activity and selectively killed U266 and RPMI 8226 myeloma cells in a dose-dependent manner, with minimal toxicity to normal cells. Additionally, gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) immune profiling using the LM22 signature suggested that HDAC6 participates in microenvironmental remodeling by modulating cell adhesion-mediated resistance and orchestrating an immunosuppressive niche characterized by monocyte depletion. This study highlights for the first time the critical role of HDAC6 in TIIA-mediated antimyeloma activity and provides novel mechanistic insights and potential targeted therapeutic strategies for the treatment of MM. - Source: PubMed
Gao JianChu JiawenLi Pengpeng - Primary cilia are essential microtubule-based sensory organelles, and their dysfunction has been increasingly linked to metabolic stress. However, the underlying molecular mechanisms remain poorly understood. Herein, we reveal that ciliary defects in retinal photoreceptors and renal tubules exacerbate tissue damage during the progression of diabetic complications. Under hyperglycemic stress, protein arginine methyltransferase 1 (PRMT1) and histone deacetylase 6 (HDAC6) are significantly upregulated in both retinal and renal tissues. Genetic ablation of either enzyme effectively preserves ciliary architecture and restores organ function in diabetic mice. Mechanistically, PRMT1 localizes to the basal body, where it interacts with and methylates HDAC6 at arginine 16, consequently enhancing HDAC6 stability. In turn, HDAC6 mediates the deacetylation of PRMT1 at lysine 128, which elevates PRMT1 protein levels. This mutual modification crosstalk establishes a pathological positive feedback loop that stabilizes a pro-disassembly complex at the basal body, thereby potentiating ciliary impairment and expediting the progression of diabetic complications. Pharmacological inhibition of the PRMT1-HDAC6 loop significantly attenuates the pathological features of both diabetic retinopathy and nephropathy. Collectively, our findings uncover a reciprocal regulatory mechanism mediated by deacetylation and arginine methylation that drives cilium disassembly under hyperglycemic stress, providing promising therapeutic targets for the treatment of metabolic ciliopathies. - Source: PubMed
Publication date: 2026/09/03
Ran JieWei ChangfengYang YangZhang YufeiGuo GuizhiMa NanYin LongFan HongjunLi JingruiGuo HengZhang RenshuaiWang RunaLi DengwenLiu Min