PXD021217-2

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	2020-08-31
AnnouncementXML	Submission_2020-11-24_22:40:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Imre
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]

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

Fumiyo Ikeda
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
Richard Imre
contact affiliation	IMBA - Institute of Molecular Biotechnology
contact email	imre@imp.ac.at
dataset submitter

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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