Identification Of Acetylated Lysine Residues On The ER Chaperone BiP

[摘要] Alzheimer;;s disease (AD) pathogenesis involves the abnormal production of a small peptidecalled Abeta. The rate-limiting enzyme for the generation of Abeta is BACEl and, as such, its downregulation decreases Abeta levels. Dr. Puglielli;;s laboratory has recently identified new aspects of BACE 1 metabolism that involve transient acetylation in the lumen of the ER and deacetylation in the Golgi apparatus. While dissecting the biochemical machinery responsible for the transient acetylation of nascent BACEl, Dr. Puglielli and co-workers have discovered that the ER-based chaperone BiP -vitally important for cellular and ER homeostasis- also undergoes lysine acetylation. The purpose of this project was to identify the lysine residues that undergoacetylation on BiP, and future experiments using mutagenesis strategies will investigate how theacetylation status of BiP affects its cellular functions. Here, we show that six acetylated lysine residues were identified: Lys81, Lys154, Lys164, Lys213, Lys585 and Lys621.

[发布机构] University of Wisconsin

[效力级别] Education and Clinical Center (GRECC)

[关键词] Geriatric Research;Education and Clinical Center (GRECC);Genetics