Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies.

ABSTRACT: Protein chaperones play a critical role in proteostasis. The activity of the major endoplasmic reticulum chaperone BiP (GRP78) is regulated by Fic-mediated AMPylation during resting states. By contrast, during times of stress, BiP is deAMPylated. Here, we show that excessive AMPylation by a constitutively active Fic^E247G mutant is lethal in Drosophila This lethality is cell-autonomous, as directed expression of the mutant Fic^E247G to the fly eye does not kill the fly but rather results in a rough and reduced eye. Lethality and eye phenotypes are rescued by the deAMPylation activity of wild-type Fic. Consistent with Fic acting as a deAMPylation enzyme, its activity was both time- and concentration-dependent. Furthermore, Fic deAMPylation activity was sufficient

SUBMITTER: Casey AK 

PROVIDER: S-EPMC5743091 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature