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.

蛋白质AMPylation（使用ATP作为供体将AMP残基共价附于氨基酸侧链）是一种翻译后修饰（PTM），人们越来越认为它与正常细胞和病理细胞信号转导都相关。在后生动物中，由包含cAMP（fic）域的AMPylase（负责AMPylation的酶）诱导的单丝化纤丝副本优先修饰一组专用靶标，并有助于感知细胞应激及其调控。致病细菌可以利用真核靶蛋白的AMPylation重组宿主细胞信号传导机制，以支持其繁殖和生存。我们审查了后生动物的内源性和寄生蛋白AMPylation，并总结了目前有关含fic域的AMPylase如何促进细胞蛋白水解的观点。