HDAC3: A Potential Drug Target and Biomarker (G8841)

Target Name: HDAC3

NCBI ID: G8841

HDAC3: A Potential Drug Target and Biomarker

Human DNA damage repair is a crucial process that ensures the stability of genetic information. DNA double-strand breaks, which can occur due to various factors, can lead to genetic mutations, including those that cause diseases such as cancer. One of the key enzymes Involved in DNA repair is the deacetylase enzyme HDAC3.

In this article, we will discuss HDAC3, its function in the DNA repair process, and its potential as a drug target and biomarker.

Function of HDAC3

HDAC3 is a protein that belongs to the HDAC family of enzymes. This family of enzymes is known for its role in the regulation of histone modifications, which are important for various cellular processes, including cell division, growth, and differentiation.

HDAC3 is primarily involved in the process of DNA double-strand break repair. When a double-strand break occurs in the DNA, the cell's repair machinery must recognize the break and attempt to repair it. HDAC3 is one of the enzymes that helps to facilitate this process.

HDAC3 functions by targeting the DNA double-strand break and recruiting a chaperone enzyme, called DNA-binding protein (DNBP), to the break. Once the DNBP is recruited, HDAC3 works to remove the damaged phosphate groups from the ends of the broken DNA strands, allowing the repair machinery to recognize and replace the damaged bonds.

HDAC3 is also involved in the regulation of gene expression, which is critical for the proper function of many cellular processes. By modulating the activity of other enzymes, HDAC3 can control the levels of various proteins in the cell, including those involved in cell growth, differentiation, and apoptosis.

Potential as a Drug Target

The potential use of HDAC3 as a drug target is due to its involvement in the regulation of various cellular processes, including DNA repair, gene expression, and cell survival.

HDAC3 has been shown to play a role in the development and progression of various diseases, including cancer. For example, studies have shown that HDAC3 is involved in the regulation of the growth and survival of cancer cells. By inhibiting the activity of HDAC3, researchers have found that they can significantly reduce the growth and survival of cancer cells.

Additionally, HDAC3 has also been shown to play a role in the regulation of cellular aging. As cells age, they undergo a variety of changes that can lead to the development of age-related diseases, including Alzheimer's disease and other forms of cognitive impairment.

HDAC3 has been shown to be involved in the regulation of these processes, and therefore, it has great potential as a drug target. Researchers are currently working to develop small molecules that can inhibit the activity of HDAC3 and use it as a drug treatment for various diseases.

Potential as a Biomarker

HDAC3 may also be used as a biomarker for certain diseases. For example, HDAC3 has been shown to be involved in the regulation of various cellular processes, including the regulation of cell death.

Studies have shown that HDAC3 plays a role in the regulation of cell death, and that its activity can be affected by various factors, including the levels of stress and damage in the cell. Therefore, HDAC3 may be used as a biomarker for stress-induced cell death, such as cancer cells that have been exposed to stressors.

HDAC3 may also be used as a biomarker for certain neurological disorders, such as Alzheimer's disease. The accumulation of damaged DNA in the brain is a hallmark of Alzheimer's disease, and HDAC3 has been shown to be involved in the regulation of the accumulation of

Protein Name: Histone Deacetylase 3

Functions: Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:23911289, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28497810, PubMed:28167758). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:23911289). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293)

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