PXD011513-2

PXD011513 is an original dataset announced via ProteomeXchange.

Title	Proteomics-based identification of ISG15 modification sites during Listeria monocytogenes infection
Description	ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity, however its precise mechanism of action during viral or bacterial infection remains elusive. We previously found that ISG15 restricts Listeria infection both in vitro and in vivo and identified ISGylated proteins that could be responsible for the protective effect. Here, we endeavored to map the in vivo ISGylome following Listeria infection to mechanistically elucidate the function of ISG15 in host defense. To do so we combined a genetic approach employing a murine model of deregulated ISGylation with quantitative proteomics of immune-enriched endogenous ISG15 modification sites. In this way, we mapped 930 ISG15 sites in 438 proteins. In addition, we also quantified protein level changes in the host proteome following infection. Gene ontology analysis revealed that ISGylated proteins were mostly enriched in proteins which alter cellular metabolic processes, including four upstream modulators of the catabolic and antibacterial pathway of autophagy. Structural analysis further revealed that a number of ISG15 modifications can occur at catalytic sites or dimerization interfaces of enzymes. Finally, we showed that animals and cells with deregulated ISGylation have increased infection-induced autophagy through the modification of mTOR, WIPI2, and AMBRA1. Taken together, these findings ascribe a putative role of ISGylation to temporarily reprogram organismal metabolism following infection through direct modification of a variety of enzymes in the liver.
HostingRepository	PRIDE
AnnounceDate	2019-11-28
AnnouncementXML	Submission_2020-01-13_05:24:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Impens Francis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitinylated lysine; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-29 08:28:20	ID requested
1	2019-11-28 02:42:13	announced
⏵ 2	2020-01-13 05:24:11	announced	2020-01-13: Updated publication reference for PubMed record(s): 31772204.

Zhang Y, Thery F, Wu NC, Luhmann EK, Dussurget O, Foecke M, Bredow C, Jim, é, nez-Fern, á, ndez D, Leandro K, Beling A, Knobeloch KP, Impens F, Cossart P, Radoshevich L, The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection. Nat Commun, 10(1):5383(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: ISG15, Ubiquitin-like modification, Listeria infection, mice

Francis Impens
contact affiliation	VIB Proteomics Core VIB-UGent Center for Medical Biotechnology UGent Department of Biomolecular Medicine
contact email	francis.impens@vib-ugent.be
lab head
Impens Francis
contact affiliation	VIB Proteomics Expertise Center
contact email	francis.impens@vib-ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011513
     1. Label: PRIDE project
     2. Name: Proteomics-based identification of ISG15 modification sites during Listeria monocytogenes infection