Premium
Identification of the first two ER/ERGIC‐based lysine acetyltransferases that are involved in the post‐translational regulation of nascent BACE1
Author(s) -
Puglielli Luigi,
Ko Mi Hee
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.605.2
Subject(s) - acetylation , endoplasmic reticulum , acetyltransferase , acetyltransferases , lysine , golgi apparatus , biochemistry , chemistry , histone acetyltransferases , chloramphenicol acetyltransferase , microbiology and biotechnology , biology , gene expression , gene , amino acid , promoter
Folding of newly synthesized membrane proteins in the endoplasmic reticulum (ER) is enhanced by enzymes that modify, either temporally or definitively, the protein. Our group has shown that the lipid second messenger ceramide regulates the molecular stability of the β‐site APP cleaving enzyme 1 (BACE1) by affecting a transient form of lysine acetylation in the ER/Golgi system (Biochem J 2007; EMBO J 2006; J Biol Chem 2003). Specifically, nascent BACE1 is initially acetylated in the lumen of the ER and then deacetylated by a Golgi‐based deacetylase. Here we report the identification of the first two ER/ERGIC‐based lysine acetyltransferases (ATase1 and ATase2). Transfection of ATase1 or ATase2 into CHO cells increased the acetyl‐CoA:lysine acetyltransferase activity recovered from cell lysates. Subcellular fractionation studies showed an ER/ERGIC localization, overlapping with the compartments where the acetylation of BACE1 occurs. When compared to control, ER/ERGIC fractions from ATase1 and ATase2 cells showed increased acetyltransferase activity. Affinity‐purified ATase1 and ATase2 were both able to acetylate BACE1 in vitro and in vivo . Finally, overexpression of ATase1 and/or ATase2 resulted in stabilization and increased steady‐state levels of BACE1. In conclusion, we have identified the first two ER/ERGIC‐based acetyltransferases involved in the molecular stabilization of nascent BACE1.