Drug Target and Biomarker: PTGS2 (COX-2) (G5743)

NCBI ID: G5743

PTGS2

Drug Target and Biomarker: PTGS2 (COX-2)

The cyclooxygenase (COX) pathway consists of two isoforms, COX-1 and COX-2. These enzymes convert arachidonic acid into prostaglandins (PGs) like prostaglandin E2 (PGE2) and prostaglandin H2 (PGH2).

Activation of COX-2, along with nuclear factor-kappaB (NF-kappaB) and COX-1, occurs in response to vascular injury. This activation leads to increased production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL-1 and IL-6), as well as prostanoids like PGE2 and PGH2. Inhibition of COX-2, COX-1, and NF-kappaB by nonsteroidal anti-inflammatory drugs (NSAIDs) can block the production of these inflammatory mediators.

In the context of infants, there is an upregulation of PTGS2 (COX-2) in monocytes of HIV-unexposed (HU) infants compared to HIV-exposed uninfected (HEU) infants. This suggests that dampened PTGS2 expression may be a specific effect observed in HEU monocytes.

Under heat stress (HS) conditions, PTGS2 (COX-2) expression is stimulated along with the P38 MAPK and NF-kB pathways, potentially modulating the expression of TGF-beta. However, alpha-lipoic acid (ALA) inhibits the expression of PTGS2 (COX-2) and TGF-beta mRNA expression induced by HS.

Compound K (CK) has been found to suppress the expression of COX-2 in response to UVB-induced damage in the skin. It also affects other pathways related to photoaging, skin hydration, and melanogenesis, including ERK and JNK activity.

Overall, these viewpoints highlight the role of PTGS2 (COX-2) in inflammation, vascular injury, neonatal development, heat stress response, and skin-related processes.
Based on the provided context information, PTGS2 (synonymous with COX-2) plays a crucial role in the tumor microenvironment and tumor progression. The tumor microenvironment consists of various cell types, including stromal, endothelial, inflammatory, and immune cells. These cells release mediators, cytokines, and growth factors that support tumor progression. EGF and PGE2 activate EGFR, leading to its internalization via dynamin-dependent Clathrin and Caveolin endocytosis. Importin beta1 then transports EGFR into the nucleus, where it interacts with STAT3 and other transcription factors (TF).

Within the nucleus, nuclear EGFR promotes the transcription of specific genes, including CCND1, PTGS2, MYC, and NOS. This process ultimately leads to increased tumor cell proliferation. The expression of nuclear EGFR and its associated gene signature have been linked to poor prognosis in non-small cell lung cancer (NSCLC) and may serve as a biomarker for patient outcomes and treatment selection.

In conclusion, PTGS2 (COX-2) is involved in the complex network of signaling within the tumor microenvironment. Its activation, along with EGF and PGE2, leads to the internalization and nuclear transportation of EGFR. This nuclear EGFR then interacts with transcription factors to promote the expression of specific genes involved in tumor cell proliferation. Understanding the role of PTGS2 and nuclear EGFR may have implications for prognostic assessment and treatment strategies in NSCLC.

Protein Name: Prostaglandin-endoperoxide Synthase 2

Functions: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:11939906, PubMed:19540099). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)

The "PTGS2 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 PTGS2 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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