Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies.
J Biol Chem
; 292(51): 21193-21204, 2017 12 22.
Article
em En
| MEDLINE
| ID: mdl-29089387
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 FicE247G mutant is lethal in Drosophila This lethality is cell-autonomous, as directed expression of the mutant FicE247G 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 to suppress the AMPylation activity mediated by the constitutively active FicE247G mutant in Drosophila S2 lysates. Further, we show that the dual enzymatic activity of Fic is, in part, regulated by Fic dimerization, as loss of this dimerization increases AMPylation and reduces deAMPylation of BiP.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monofosfato de Adenosina
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Processamento de Proteína Pós-Traducional
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Proteínas de Drosophila
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Proteínas de Choque Térmico
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Nucleotidiltransferases
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article