Cyclooxygenase 2: protein-protein interactions and posttranslational modifications. Physiol Genomics 2017 Nov 01;49(11):667-681
Date
09/25/2017Pubmed ID
28939645Pubmed Central ID
PMC5792139DOI
10.1152/physiolgenomics.00086.2017Scopus ID
2-s2.0-85044391314 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Numerous studies implicate the cyclooxygenase 2 (COX2) enzyme and COX2-derived prostanoids in various human diseases, and thus, much effort has been made to uncover the regulatory mechanisms of this enzyme. COX2 has been shown to be regulated at both the transcriptional and posttranscriptional levels, leading to the development of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX2 inhibitors (COXIBs), which inhibit the COX2 enzyme through direct targeting. Recently, evidence of posttranslational regulation of COX2 enzymatic activity by s-nitrosylation, glycosylation, and phosphorylation has also been presented. Additionally, posttranslational regulators that actively downregulate COX2 expression by facilitating increased proteasome degradation of this enzyme have also been reported. Moreover, recent data identified proteins, located in close proximity to COX2 enzyme, that serve as posttranslational modulators of COX2 function, upregulating its enzymatic activity. While the precise mechanisms of the protein-protein interaction between COX2 and these regulatory proteins still need to be addressed, it is likely these interactions could regulate COX2 activity either as a result of conformational changes of the enzyme or by impacting subcellular localization of COX2 and thus affecting its interactions with regulatory proteins, which further modulate its activity. It is possible that posttranslational regulation of COX2 enzyme by such proteins could contribute to manifestation of different diseases. The uncovering of posttranslational regulation of COX2 enzyme will promote the development of more efficient therapeutic strategies of indirectly targeting the COX2 enzyme, as well as provide the basis for the generation of novel diagnostic tools as biomarkers of disease.
Author List
Alexanian A, Sorokin AAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCyclooxygenase 2
Disease
Humans
Models, Biological
Protein Binding
Protein Interaction Maps
Protein Processing, Post-Translational
