HDAC6: A Drug Target / Disease Biomarker (G10013)
HDAC6: A Drug Target / Disease Biomarker
High-throughput screening (HTS) assays have revolutionized drug discovery by enabling rapid and efficient identification of potential drug targets and biomarkers. One of the most promising targets in the field is HDAC6, a gene encoding a protein that plays a crucial role in the regulation of histone dynamics and is mutated in various diseases, including cancer. In this article, we will discuss the biology of HDAC6, its potential as a drug target, and the current research efforts aimed at its development as a therapeutic agent.
The histone is a protein that plays a critical role in the regulation of gene expression and is composed of four histone proteins (H1, H2A, H2B, and H3). Histones are loaded onto the DNA template during the process of transcription and then play a crucial role in the condensation of chromatin during DNA replication. HDAC6 is a member of the HDAC family, which includes a variety of proteins that share similar domain structures and functions in the regulation of histone dynamics.
Mutations in the HDAC6 gene have been observed in various diseases, including cancer, neurodegenerative diseases, and psychiatric disorders. These mutations can lead to alterations in the structure and function of the HDAC6 protein, leading to changes in the regulation of histone dynamics and the development of disease. For example, a missense mutation in the HDAC6 gene has been associated with the development of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
In addition to its role in the regulation of histone dynamics, HDAC6 is also a potential drug target because of its unique structure and function. HDAC6 is a 24-kDa protein that contains a unique N-terminal region that includes a conserved Asp and a unique Glu residue. This unique structure makes it an attractive target for small molecules, antibodies, or other therapeutic agents that can modulate its activity and function.
Several studies have demonstrated the potential of HDAC6 as a drug target. For example, a variety of small molecules have been shown to interact with HDAC6 and modulate its activity. These molecules include inhibitors of the HDAC6 enzyme, as well as modulators of its activity, such as drugs that increase or decrease the levels of HDAC6 in the cells. Additionally, several studies have used high-throughput screening (HTS) assays to identify potential biomarkers for HDAC6-related diseases, such as cancer.
In addition to its potential as a drug target, HDAC6 is also a promising biomarker for various diseases. The regulation of histone dynamics is a critical process that is involved in the development and progression of many diseases, including cancer. Therefore, changes in the regulation of histone dynamics can be an attractive biomarker for diseases that are characterized by alterations in the histone structure and/or function.
Several studies have used HTS assays to identify potential biomarkers for HDAC6-related diseases, including cancer. For example, a study by Srivastava and colleagues (8) used HTS assays to identify potential biomarkers for HDAC6-positive breast cancer. The authors found that several compounds, including inhibitors of the HDAC6 enzyme, had the potential to serve as biomarkers for this disease. Similarly, a study by Zhang and colleagues (9) used HTS assays to identify potential biomarkers for HDAC6-positive lung cancer. The authors found that several compounds, including small molecules and antibodies, had the potential to serve as biomarkers for this disease.
In conclusion, HDAC6 is a gene encoding a protein that plays a crucial role in the regulation of histone dynamics and is mutated in various diseases. Its unique structure and function make it an attractive target for small molecules, antibodies, or other therapeutic agents that can modulate its activity and function. In addition to its potential as a drug target, HDAC6 is also a promising biomarker for various diseases, including cancer. Several studies have used HTS assays to identify potential
Protein Name: Histone Deacetylase 6
Functions: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10220385). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:10220385). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:10220385). In addition to histones, deacetylates other proteins: plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (PubMed:12024216, PubMed:20308065). Required for cilia disassembly; via deacetylation of alpha-tubulin (PubMed:17604723). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (PubMed:17846173). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy (PubMed:17846173)
More Common Targets
HDAC7 | HDAC8 | HDAC9 | HDC | HDDC2 | HDDC3 | HDGF | HDGFL1 | HDGFL2 | HDGFL3 | HDHD2 | HDHD3 | HDHD5 | HDHD5-AS1 | HDLBP | HDX | Heat Shock Protein 27 (Hsp27) | Heat shock protein 70 | Heat shock protein 90 | HEAT2 | HEATR1 | HEATR3 | HEATR4 | HEATR5A | HEATR5B | HEATR6 | HEATR6-DT | HEATR9 | HEBP1 | HEBP2 | HECA | HECTD1 | HECTD2 | HECTD2-AS1 | HECTD3 | HECTD4 | HECW1 | HECW2 | Hedgehog Protein | HEG1 | HEIH | HELB | HELLS | HELQ | HELT | HELZ | HELZ2 | Heme Oxygenase (HO) | HEMGN | HEMK1 | Hemoglobin A-2 (HbA-2) | Hemoglobulin A (HbA) | HENMT1 | HEPACAM | HEPACAM2 | HEPH | HEPHL1 | HEPN1 | HER (erbB) | HERC1 | HERC2 | HERC2P10 | HERC2P2 | HERC2P3 | HERC2P4 | HERC2P5 | HERC2P7 | HERC2P8 | HERC2P9 | HERC3 | HERC4 | HERC5 | HERC6 | HERPUD1 | HERPUD2 | HES1 | HES2 | HES3 | HES4 | HES5 | HES6 | HES7 | HESX1 | Heterogeneous nuclear ribonucleoprotein complex | HEXA | HEXA-AS1 | HEXB | HEXD | HEXIM1 | HEXIM2 | Hexokinase | HEY1 | HEY2 | HEY2-AS1 | HEYL | HFE | HFM1 | HGC6.3 | HGD | HGF