PXD021217-3

PXD021217 is an original dataset announced via ProteomeXchange.

Title	Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling
Description	HOIP, the catalytic component of the Linear Ubiquitin chain Assembly Complex (LUBAC), is a critical regulator of inflammation. However, how HOIP itself is regulated to control inflammatory responses is unclear. Here, we discover that site-specific ubiquitination of K784 within HOIP promotes Tumour Necrosis Factor (TNF)-induced inflammatory signalling. A HOIP K784R mutant is catalytically active but shows reduced induction of an NF-B reporter relative to wild type HOIP. HOIP K784 is evolutionarily conserved, equivalent to HOIP K778 in mice. We generated HoipK778R/K778R knockin mice, which show no overt developmental phenotypes; however, in response to TNF, HoipK778R/K778R mouse embryonic fibroblasts display suppressed NF-B activation and increased apoptotic markers. On the other hand, HOIP K778R enhances the TNF-induced formation of TNFR complex II, and an interaction between TNFR complex II and LUBAC. Loss of the LUBAC component SHARPIN leads to embryonic lethality in HoipK778R/K778R mice, which is rescued by knockout of TNFR1. We propose that site-specific ubiquitination of HOIP regulates a LUBAC-dependent switch between survival and apoptosis in TNF-signalling.
HostingRepository	PRIDE
AnnounceDate	2023-05-14
AnnouncementXML	Submission_2023-05-14_14:02:00.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	RichardImre
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature tetrapeptidyl lysine; ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-31 01:54:45	ID requested
1	2020-08-31 02:31:27	announced
2	2020-11-24 22:40:51	announced	2020-11-25: Updated publication reference for PubMed record(s): 33215740.
⏵ 3	2023-05-14 14:02:01	announced	2023-05-14: Updated project metadata.

Fennell LM, Gomez Diaz C, Deszcz L, Kavirayani A, Hoffmann D, Yanagitani K, Schleiffer A, Mechtler K, Hagelkruys A, Penninger J, Ikeda F, Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling. EMBO J, 39(24):e103303(2020) [pubmed]

ProteomeXchange project tag: EPIC-XS

submitter keyword: Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling

FumiyoIkeda
contact affiliation	Professor, Division of Inflammation and Proteostasis, Medical Institute of Bioregulation (MIB), Kyushu University Address: 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Office phone: +81-(0)92-642-4769 Website: https://ikedalab.bioreg.kyushu-u.ac.jp/ Twitter:@IkedaResearch
contact email	fumiyo.ikeda@bioreg.kyushu-u.ac.jp
lab head
RichardImre
contact affiliation	IMBA - Institute of Molecular Biotechnology
contact email	imre@imp.ac.at
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/08/PXD021217

PRIDE project URI

• PRIDE
  1. PXD021217
     1. Label: PRIDE project
     2. Name: Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling