cox2

PTGS2, also known as COX-2, is s component of Prostaglandin-endoperoxide synthase (PTGS). PTGS, also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. PTGS2 is overexpressed in many cancers. The overexpression of PTGS2 along with increased angiogenesis and GLUT-1 expression is significantly associated with gallbladder carcinomas. Furthermore the product of COX-2, PGH2 is converted by prostaglandin E2 synthase into PGE2, which in turn can stimulate cancer progression. Consequently inhibiting COX-2 may have benefit in the prevention and treatment of these types of cancer. PTGS2 is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. It mediates the formation of prostaglandins from arachidonate and may have a role as a major mediator of inflammation and or a role for prostanoid signaling in activity-dependent plasticity.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha beta, DDX58 RIG-I, TNFSF10 TRAIL, ZBP1, OAS1 2, PIAS1 GBP, EIF2AK2 PKR and RSAD2 viperin; antibacterial response, such as NOS2 INOS; anti-proliferative response, such as p53 TP53, LOX and CDKN1A; apoptosis, such as BBC3 PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A B and IL15, PTGS2 COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ POLH; MHC class I expression, such as TAP1, PSMB9 LMP2, PSME1 PA28A, PSME2 PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1 IRG1. Represses genes involved in anti-proliferative response, such as BIRC5 survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53 TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53 TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.