SIRT2: A Potent Drug Target and Biomarker (G22933)

Target Name: SIRT2

NCBI ID: G22933

SIRT2

SIRT2: A Potent Drug Target and Biomarker

Sirtuins, also known as NAD+-dependent enzymes, are proteins that regulate gene expression and cellular metabolic processes within cells. Sirtuins play important biological roles in organisms, including maintaining cellular homeostasis, participating in cell cycle regulation, and regulating apoptosis. Among them, SIRT2 is an important Sirtuin that plays a key role in various physiological processes. In recent years, researchers have discovered that SIRT2 has broad application prospects in the field of drug research and development and is of high value as a drug target or biomarker.

Discovery and research of SIRT2

The discovery of SIRT2 originated from the study of intracellular metabolic processes. Scientists discovered the Sirtuin family in the mid-1990s. The proteins of this family have similar functions in cells, including regulating gene expression, phosphorylation, oxidative modification, etc. Among these proteins, SIRT2 was the first member to be discovered. The discovery of SIRT2 marks a new field of biomedical research and provides new ideas for studying the role of Sirtuins in organisms.

The mechanism of action of SIRT2 in vivo

The mechanism of action of SIRT2 in organisms is very complex and involves multiple biological processes. Listed below are some of the main functions of SIRT2 in cells:

1. Maintenance of cellular homeostasis

SIRT2 participates in a variety of cellular homeostasis regulation processes in cells, including pH regulation, ion balance, redox status, etc. SIRT2 maintains the stability of cellular homeostasis through a series of complex metabolic pathways and provides cells with a suitable living environment.

2. Cell cycle regulation

SIRT2 plays an important role in cell cycle regulation. The activity of SIRT2 can be reduced at different stages of mitosis, thereby participating in regulating spindle formation and stability. In addition, SIRT2 can also inhibit the polymerization of microtubules and further regulate the progression of mitosis.

3. Apoptosis

SIRT2 plays a key role in apoptosis. SIRT2 regulates the transmission of intracellular apoptosis signals through a series of complex signaling pathways, thereby participating in the regulation of apoptosis. The activity of SIRT2 is significantly reduced during cell senescence and apoptosis, providing new ideas for studying the regulation of cell senescence and apoptosis.

4. Oxidative modification

SIRT2 participates in the regulation of oxidative modification in vivo. SIRT2 participates in the regulation of intracellular redox status through a series of complex metabolic pathways, providing a stable oxidative environment for cells.

The pharmacological significance of SIRT2

SIRT2 has broad application prospects in the field of drug research and development. Studies have found that SIRT2 plays a key role in a variety of diseases, such as aging, neurodegenerative diseases, liver diseases, tumors, etc. The activity of SIRT2 can affect the onset and development of various diseases by regulating gene expression and cellular metabolic processes. Therefore, SIRT2 has become an important drug target with high clinical application value.

The biological value of SIRT2

The mechanism of action of SIRT2 in organisms is very complex, which provides an important theoretical basis for studying intracellular metabolic processes. The activity of SIRT2 plays a key role in cells and is involved in the regulation of various biological processes. For example, SIRT2 maintains the stability of cellular homeostasis by regulating intracellular pH, ion balance, and redox status; by participating in cell cycle regulation, it affects the formation and stability of spindles; by regulating cell apoptosis, it participates in cell Regulation of aging and apoptosis; by participating in the regulation of oxidative modification, it affects the stability of the intracellular redox state.

In addition, SIRT2 activity can also be used to treat a variety of diseases. Studies have found that SIRT2 plays an important role in a variety of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, etc. The activity of SIRT2 can affect gene expression and cellular metabolic processes.

Protein Name: Sirtuin 2

Functions: NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:24177535, PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy (PubMed:24177535, PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). Plays a major role in the control of cell cycle progression and genomic stability (PubMed:12697818, PubMed:17488717, PubMed:16909107, PubMed:17726514, PubMed:19282667, PubMed:23468428). Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes (PubMed:12697818, PubMed:17488717, PubMed:16909107, PubMed:17726514, PubMed:19282667, PubMed:23468428). Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis (PubMed:22014574). Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes (PubMed:23468428). Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis (PubMed:23468428). Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition (PubMed:20587414). Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function (PubMed:24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed:18332217, PubMed:18995842). Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation (PubMed:17488717). Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination (PubMed:21949390). Involved in several cellular metabolic pathways (PubMed:20543840, PubMed:21726808, PubMed:24769394). Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability (PubMed:21726808). Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage (PubMed:24769394). Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis (PubMed:20543840). Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed:20543840). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:20543840). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators

The "SIRT2 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about SIRT2 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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