The NOX family of NADPH oxidases are enzymes which function is dedicated to the production of reactive oxygen species. NOX1, a member of this family is expressed abundantly in the intestine and its disregulation could be linked to inflammatory diseases such as inflammatory bowel diseases. However, the molecular basis of NOX1 regulation remains unclear. During my thesis, I demonstrated that 1) NOXA1, the activator cytosolic subunit of the NOX1 complex, is phosphorylated and its phosphorylation prevents hyperactivation of NOX1 in order to maintain a constitutive activity which would not be too excessive. 2) phosphorylation of human NOXO1, the organizer subunit of the complex is a prerequisite of full activation of NOX1. Taken together, these results demonstrate that NOX1 is tightly regulated by phosphorylation events. By this mean, NOX1 could be involved in host immune defense of the intestine.
Regulation of the NADPH oxidase NOX1 : a crucial role of NOXA1 (NOX Activator 1) and NOXO1 (NOX Organizer 1) phosphorylation