OGT: A Potential Drug Target for Cancer and Neurodegenerative Diseases
OGT: A Potential Drug Target for Cancer and Neurodegenerative Diseases
OGT (UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit (isoform 1)) is a protein that plays a crucial role in the process of glucosaminyl transfer in the gut. It is encoded by the UCP2 gene and is expressed in the intestinal epithelial cells of the small intestine. The primary function of OGT is to transfer UDP-N-acetylglucosamine (UA) to the N-acetylglucosamine (NAG) via its active site, thereby participating in the first step of the glycosaminyl cycle. UA is a key precursor for the synthesis of NAG, which is the major determinant of the gut microbiota and has been linked to various health conditions, including cancer, neurodegenerative diseases, and systemic inflammatory diseases.
In addition to its role in the glycosaminyl cycle, OGT has been shown to have various non-coding RNA (ncRNA) profiles in the gut epithelial cells. These profiles have been associated with the regulation of gene expression, including the expression of genes involved in cell adhesion, differentiation, and inflammation.
Recent studies have also shown that OGT is involved in the regulation of gut microbiota function. OGT has been shown to play a positive role in the development and maintenance of a healthy gut microbiota, as well as in the regulation of bacterial diversity and the production of various beneficial bacteria. In addition, OGT has been shown to modulate the inflammatory response of the gut epithelial cells, thereby contributing to the regulation of gut homeostasis and the overall health of the organism.
Due to its involvement in the glycosaminyl cycle and its role in the regulation of gut microbiota function, OGT has potential as a drug target or biomarker for various diseases. One potential target for OGT is cancer, as OGT has been shown to be involved in the regulation of cell cycle progression and apoptosis in various types of cancer. In addition, OGT has also been shown to be involved in the regulation of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
Another potential target for OGT is neuroinflammation, as OGT has been shown to play a role in the regulation of inflammation in the brain and central nervous system. In addition, OGT has also been shown to be involved in the regulation of pain perception and the modulation of pain modalities.
In conclusion, OGT is a protein that has important roles in the process of glucosaminyl transfer and the regulation of the gut microbiota. Its involvement in the glycosaminyl cycle and its potential as a drug target or biomarker make it an attractive target for the development of new treatments for various diseases. Further research is needed to fully understand the functions of OGT and its potential as a drug target.
Protein Name: O-linked N-acetylglucosamine (GlcNAc) Transferase
Functions: Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc) (PubMed:26678539, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:15361863). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1 (PubMed:19451179, PubMed:20200153, PubMed:21285374, PubMed:22923583, PubMed:23353889, PubMed:24474760, PubMed:26678539, PubMed:27527864, PubMed:34074792). Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539). Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3) (PubMed:22121020, PubMed:23353889). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, PubMed:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863). O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). O-glycosylates FNIP1 (PubMed:30699359). Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864)
The "OGT 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 OGT 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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