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Title: A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination

Abstract

Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents. Recent studies revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attacked 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. Following ubiquitin activation by ADP- ribosylation via a mono-ADP-ribosylation motif, ADP-ribosylated ubiquitin is cleaved by a phosphodiesterasedomainwithinSdeA,whichisconcomitantwiththelinkof phosphoribosylated ubiquitin to serine residues in the substrate. Here we demonstrate that the activity of SidEs is regulated by SidJ, another effector encoded by a gene situated in the locus coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ functions to remove ubiquitin from SidEs-modified substrates by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates. Further, the deubiquitinase activity of SidJ is essential for its role in L. pneumophila infection. Finally, the activity of SidJ is required for efficiently reducing the abundance of ubiquitinated Rab33b in infected cells within a few hours after bacterial uptake. Our results establish SidJ as a deubiquitinase that functions to impose temporal regulation of the activity of the SidE effectors. Themore » identification of SidJ may shed light on future study of signaling cascades mediated by this unique ubiquitination that also potentially regulates cellular processes in eukaryotic cells.« less

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1371993
Report Number(s):
PNNL-SA-123995
Journal ID: ISSN 1001-0602; 49531; 453040220
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Cell Research
Additional Journal Information:
Journal Volume: 27; Journal Issue: 7; Journal ID: ISSN 1001-0602
Publisher:
Shanghai Institutes for Biological Sciences
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Environmental Molecular Sciences Laboratory

Citation Formats

Qiu, Jiazhang, Yu, Kaiwen, Fei, Xiaowen, Liu, Yao, Nakayasu, Ernesto S., Piehowski, Paul D., Shaw, Jared B., Puvar, Kedar, Das, Chittaranjan, Liu, Xiaoyun, and Luo, Zhao-Qing. A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination. United States: N. p., 2017. Web. doi:10.1038/cr.2017.66.
Qiu, Jiazhang, Yu, Kaiwen, Fei, Xiaowen, Liu, Yao, Nakayasu, Ernesto S., Piehowski, Paul D., Shaw, Jared B., Puvar, Kedar, Das, Chittaranjan, Liu, Xiaoyun, & Luo, Zhao-Qing. A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination. United States. doi:10.1038/cr.2017.66.
Qiu, Jiazhang, Yu, Kaiwen, Fei, Xiaowen, Liu, Yao, Nakayasu, Ernesto S., Piehowski, Paul D., Shaw, Jared B., Puvar, Kedar, Das, Chittaranjan, Liu, Xiaoyun, and Luo, Zhao-Qing. Fri . "A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination". United States. doi:10.1038/cr.2017.66.
@article{osti_1371993,
title = {A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination},
author = {Qiu, Jiazhang and Yu, Kaiwen and Fei, Xiaowen and Liu, Yao and Nakayasu, Ernesto S. and Piehowski, Paul D. and Shaw, Jared B. and Puvar, Kedar and Das, Chittaranjan and Liu, Xiaoyun and Luo, Zhao-Qing},
abstractNote = {Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents. Recent studies revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attacked 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. Following ubiquitin activation by ADP- ribosylation via a mono-ADP-ribosylation motif, ADP-ribosylated ubiquitin is cleaved by a phosphodiesterasedomainwithinSdeA,whichisconcomitantwiththelinkof phosphoribosylated ubiquitin to serine residues in the substrate. Here we demonstrate that the activity of SidEs is regulated by SidJ, another effector encoded by a gene situated in the locus coding for three members of the SidE family (SdeC, SdeB and SdeA). SidJ functions to remove ubiquitin from SidEs-modified substrates by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates. Further, the deubiquitinase activity of SidJ is essential for its role in L. pneumophila infection. Finally, the activity of SidJ is required for efficiently reducing the abundance of ubiquitinated Rab33b in infected cells within a few hours after bacterial uptake. Our results establish SidJ as a deubiquitinase that functions to impose temporal regulation of the activity of the SidE effectors. The identification of SidJ may shed light on future study of signaling cascades mediated by this unique ubiquitination that also potentially regulates cellular processes in eukaryotic cells.},
doi = {10.1038/cr.2017.66},
journal = {Cell Research},
issn = {1001-0602},
number = 7,
volume = 27,
place = {United States},
year = {2017},
month = {5}
}

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