Place: 4274 Chamberlin (refreshments will be served)
Speaker: Luigi Puglielli, UW Department of Medicine
Abstract: Our group recently reported that mammalian cells are able to acetylate the Ne-lysine residue of nascent membrane proteins in the lumen of the endoplasmic reticulum (ER). This event was initially discovered while studying the mechanisms that regulate the levels of b-site APP cleaving enzyme 1 (BACE1), a type I membrane protein that is involved in the pathogenesis of AlzheimeraEuroTMs disease. However, it is now clear that this process is not limited to BACE1. In fact, other membrane and secreted proteins as well as ER-resident proteins that are involved with synthesis and folding of nascent proteins in the ER lumen are also acetylated. Here, I will describe the biochemical properties of the individual components of the ER-based acetylation machinery and their impact on different neurodegenerative diseases, including AlzheimeraEuroTMs disease and spastic paraplegias. I will also discuss the initial characterization of a newly-generated animal model showing a possible impact of the ER-based acetylation machinery on the biology of the immune system as well as the risk for cancer.