In a recent study, Dr. Chen and colleagues identified a critical role of myeloid epsins to promote atherogenesis through ubiquitin-dependent regulation of the LRP-1 receptor. They utilized elegant, myeloid-specific epsin double-knockout mouse models to define its role in atherogenesis progression and showed that epsin loss decreased atherosclerotic lesions. They investigated this pathological phenomenon at the cellular level and identified critical changes in macrophages, defined by suppression of a pro-inflammatory phenotype and enhancement of an anti-inflammatory phenotype. Further examination led to the molecular discovery that levels of LRP-1, a surface receptor that promotes an anti-inflammatory phenotype, were enhanced in the absence of myeloid epsins. Importantly, they discovered that LRP-1 and epsins interact through epsin’s ubiquitin-interacting motif. In response to oxidizied-LDL, a pro-inflammatory stimulant, LRP-1’s ubiquitination increased, which enhanced its interaction with epsins. Cytoskeleton’s ubiquitin antibody (Cat. # AUB01) was a critical reagent that was utilized to investigate the ubiquitination state of LRP-1, which provided a key finding in unraveling the mechanistic interaction and regulation of these proteins in atherogenesis. This study provides the foundation to target myeloid-specific epsins as a potential therapeutic to treat atherogenesis, and it will be interesting to see if they can regulate epsin through targeting its ubiquitin-interacting motif.
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Schematic of Atherogensis regulation through epsin’s ubiquitin-dependent interaction with LRP-1 receptors