Overexpression of ATase1 and ATase2 disrupts the secretome and causes a progeria phenotype.

ABSTRACT: Nε-lysine acetylation in the lumen of the ER requires two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. They are type II membrane proteins and belong to the larger GNAT superfamily of acetyltransferases. Their enzymatic activity is tightly coupled to the import of acetyl-CoA in the lumen of the ER by AT-1/SLC33A1. Gene duplication events involving 3q25.31 (harboring AT-1/SLC33A1) and 2p13.1 (harboring ATase1/NAT8B and ATase2/NAT8) are associated with autism spectrum disorder with intellectual disability and progeria-like dysmorphism. Here, we report the generation and phenotypic characterization of mice with systemic overexpression of ATase1 (ATase1 sTg) and ATase2 (ATase2 sTg). Overexpression of either ATase at conception was found to be lethal while overexpressio

SUBMITTER: Cheng TL 

PROVIDER: S-EPMC12423556 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature