rAMPing Up Stress Signaling: Protein AMPylation in Metazoans.

Protein AMPylation - the covalent attachment of an AMP residue to amino acid side chains using ATP as the donor - is a post-translational modification (PTM) increasingly appreciated as relevant for both normal and pathological cell signaling. In metazoans single copies of filamentation induced by cAMP (fic)-domain-containing AMPylases - the enzymes responsible for AMPylation - preferentially modify a set of dedicated targets and contribute to the perception of cellular stress and its regulation. Pathogenic bacteria can exploit AMPylation of eukaryotic target proteins to rewire host cell signaling machinery in support of their propagation and survival. We review endogenous as well as parasitic protein AMPylation in metazoans and summarize current views of how fic-domain-containing AMPylases contribute to cellular proteostasis.