A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

Cell Research
Jiazhang QiuZhao-Qing Luo

Abstract

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-ribosyltransferase 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 links phosphoribosylated ubiquitin to protein substrates. SidJ also displays classical deubiquitinase activity but does not require catalytic cysteine residues. Further, these deubiquitinase activities of SidJ are essential ...Continue Reading

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Citations

Jun 3, 2017·Cell Research·Judith A Ronau, Mark Hochstrasser
Mar 31, 2018·Nature Communications·Shangda YangLei Shi
Mar 30, 2018·FEMS Microbiology Reviews·Eric MartinezMatteo Bonazzi
Nov 4, 2017·The Journal of Cell Biology·Elias CornejoShaeri Mukherjee
Jan 30, 2018·Frontiers in Cellular and Infection Microbiology·Jiazhang Qiu, Zhao-Qing Luo
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Mar 2, 2018·Biological Reviews of the Cambridge Philosophical Society·Xiaoxiang ChengHongjie Zhang
Apr 18, 2019·Open Biology·Luca PalazzoIvan Ahel
Jul 18, 2017·Nature Reviews. Microbiology·Jiazhang Qiu, Zhao-Qing Luo
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Oct 28, 2021·Nature Communications·Michael AdamsSagar Bhogaraju

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Methods Mentioned

BETA
deubiquitinases
ubiquitination
GTPases
deubiquitination
affinity
pull-down
GTPase
transfection
immunoprecipitation

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