PXD043553

PXD043553 is an original dataset announced via ProteomeXchange.

Title	USP16 is an ISG15 cross-reactive deubiquitinase targeting a subset of metabolic pathway-related proteins
Description	The ubiquitin-like modifier ISG15 can modulate host and viral proteins to restrict viral and microbial infections, and act as a cytokine. Its expression and conjugation are strongly up-regulated by type I interferons. Here we identify the deubiquitinating enzyme USP16 as an ISG15 cross-reactive protease. Ubiquitin-specific protease 16 (USP16) was found to react with an ISG15 activity-based probe in pull-down experiments using chronic myeloid leukaemia-derived human cells (HAP1). Supporting this finding, recombinant USP16 cleaved pro-ISG15 and ISG15 iso-peptide linked model substrates in vitro, as well as ISGylated substrates present in cell lysates. Moreover, the interferon-induced stimulation of ISGylation in human HAP1 cells was increased by knockdown or knockout of USP16. Depletion of USP16 did not affect interferon signaling, and interferon treatment did not affect USP16 expression or enzymatic activity either. A USP16-dependent ISG15 interactome was established by anti-ISG15 immunoprecipitation mass spectrometry (IP-MS), which indicated that the deISGylating function of USP16 may regulate metabolic pathways involving GOT1, ALDOA, SOD1 and MDH1, all of which were further confirmed to be deISGylated by USP16 in HEK293T cells. Together, our results indicate that USP16 may contribute to regulating the ISGylation status of a subset of proteins related to metabolism during type I interferon responses.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:40.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adan Pinto-Fernandez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-05 03:49:18	ID requested
1	2023-11-17 02:44:42	announced
⏵ 2	2024-10-22 06:14:41	announced	2024-10-22: Updated project metadata.

10.1073/PNAS.2315163120;

submitter keyword: USP16, Innate Immunity, Metabolic Enzyme, ISG15

Adán Pinto-Fernández
contact affiliation	COI-NDM (University of Oxford)
contact email	adan.pintofernandez@ndm.ox.ac.uk
lab head
Adan Pinto-Fernandez
contact affiliation	University of Oxford
contact email	adan.pintofernandez@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043553
     1. Label: PRIDE project
     2. Name: USP16 is an ISG15 cross-reactive deubiquitinase targeting a subset of metabolic pathway-related proteins