PXD020909

PXD020909 is an original dataset announced via ProteomeXchange.

Title	USP22 controls necroptosis by regulating receptor interacting protein kinase 3 ubiquitination
Description	Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of monoubiquitination from histone H2B, thereby regulating gene transcription. However, novel roles for USP22 have recently emerged, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in a variety of tumor cell lines. Loss of USP22 expression significantly delays TNF/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNF-mediated NF-B activation or extrinsic apoptosis. Mass-spectrometric ubiquitin remnant profiling identified lysine 518 of Receptor-interacting protein kinase 3 (RIPK3) as USP22-dependent ubiquitination target during necroptosis induction. Mutation of K518 in RIPK3 reduced necroptosisassociated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of ubiquitination as crucial regulator of necroptotic cell death.
HostingRepository	PRIDE
AnnounceDate	2021-01-04
AnnouncementXML	Submission_2021-01-04_04:56:25.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-14 02:45:29	ID requested
⏵ 1	2021-01-04 04:56:26	announced

Roedig J, Kowald L, Juretschke T, Karlowitz R, Ahangarian Abhari B, Roedig H, Fulda S, Beli P, van Wijk SJ, USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination. EMBO Rep, 22(2):e50163(2021) [pubmed]

submitter keyword: cancer/MLKL/posttranslational modifications/RIPK1/ubiquitin hydrolase

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020909
     1. Label: PRIDE project
     2. Name: USP22 controls necroptosis by regulating receptor interacting protein kinase 3 ubiquitination