Assessing Jagged1 redox signalling mechanisms following quantitative analysis of the endothelial redox proteome

Dysregulated angiogenesis is a common feature of cardiovascular disease and cancer. Oxidative stress and redox signalling play a crucial role in the control of angiogenesis. At the molecular level this regulation occurs through cysteine thiol modifications on proteins which has the propensity to alter their physiochemical properties. A key redox modification regulating protein function is S-glutathionylation. This reversible modification is enzymatically removed by Glutaredoxin1 (GLRX1). Previous in vivo work highlighted a role for GLRX1 in neovascularisation and angiogenesis. However, the full range of redox-sensitive proteins regulating angiogenesis is not fully understood. This study aimed to uncover redox-sensitive proteins involved in angiogenesis and establish a set of candidate proteins for downstream investigation. Following bioinformatic analysis of candidates, Jagged1 (JAG1) was selected as an interesting and novel target for further investigation. JAG1 is a transmembrane protein that regulates vascular sprouting through cell-cell interactions. Additionally, proteolytic cleavage of JAG1 produces an intracellular (ICD) fragment which regulates transcription.