Lysine acetylation in the lumen of the ER: A novel and essential function under the control of the UPR

摘要: The N(e)-amino group of lysine residues can be transiently modified by the addition an acetyl group. Recognized functions N(e)-lysine acetylation include regulation activity, molecular stabilization and conformational assembly a protein. For more than forty years was thought to occur only in cytosol nucleus. Targets included cytoskeletal-associated proteins as well transcription factors, histone involved DNA recombination repair. However, 2007 we reported that type I membrane protein pathogenesis Alzheimer's disease acetylated on e amino seven while transiting along secretory pathway. Surprisingly, occurred lumen endoplasmic reticulum (ER) forcing us reconsider old paradigms. Indeed, if ER, then all essential biochemical elements reaction must available organelle. Follow-up studies revealed existence ER-based acetyl-CoA:lysine acetyltransferases transporter translocates acetyl-CoA from into ER lumen. Large-scale proteomics showed list substrates machinery includes both resident proteins. Finally, genetic this is tightly linked human diseases. Here, describe these exciting findings recent cellular advances, discuss possible impact physiology pathology.