A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

Jiazhang Qiu;Xiaoyun Liu;Zhao-Qing Luo;Kaiwen Yu;Xiaowen Fei;Yao Liu;Ernesto S Nakayasu;Paul D Piehowski;Jared B Shaw;Kedar Puvar;Chittaranjan Das

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2017(027)007

【摘要】Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents.Recent studies have revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attack several small GTPases associated with the endoplasmic reticulum by a novel ubiquitination mechanism that does not require the E1 and E2 enzymes of the host ubiquitination machinery.In this case,ubiquitin is first activated by ADP-ribosylation at Arg42 by a mono-ADP-ribosyitransferase activity;the intermediate is then cleaved by a phosphodiesterase activity also residing within SdeA,concomitant with the attachment of ubiquitin to serine residues of substrate proteins via a phosphoribosyl linker.Here we demonstrate that the effect of SidEs is antagonized by SidJ,an effector encoded by a gene situated in the locus coding for three members of the SidE family (SdeC,SdeB and SdeA).SidJ reverses ubiquitination of SidEs-modified substrates by cleaving the phosphodiester bond that finks phosphoribosylated ubiquitin to protein substrates.SidJ also