PXD024355

PXD024355 is an original dataset announced via ProteomeXchange.

Title	N4BP1 is a unique, dimerization-dependent linear ubiquitin reader that regulates TNFR1 signalling through linear ubiquitin binding and Caspase-8-dependent processing
Description	Signalling through TNFR1 modulates proinflammatory gene transcription and programmed cell death, and its impairment causes autoimmune diseases and cancer. NEDD4 binding protein 1 (N4BP1) was recently identified as a critical suppressor of proinflammatory cytokine production1, whose mode of action remained unknown. Here, we show that N4BP1 is a novel linear ubiquitin receptor that negatively regulates NFB signalling by its unique dimerization-dependent ubiquitin-binding module. N4BP1 homo-oligomerization strategically positions two non-selective ubiquitin-binding domains, ensuring exclusive recognition of linear ubiquitin. Under proinflammatory conditions, N4BP1 is recruited to the nascent TNFR1 signalling complex where it, through linear ubiquitin binding, regulates stability of the TNFR1 signalling complex and duration of proinflammatory signalling. N4BP1 deficiency accelerates TNF-induced cell death by increasing complex II assembly. Under proapoptotic conditions, Caspase-8 mediates proteolytic processing of N4BP1 and the resulting cleavage fragment of N4BP1, which retains the ability to bind linear ubiquitin, is rapidly degraded by the 26S proteasome, accelerating apoptosis. In summary, our findings demonstrate that N4BP1 dimerization creates a unique linear ubiquitin reader that ensures timely and coordinated regulation of TNFR1-mediated inflammation and cell death.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:40:49.403.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katarzyna Kliza
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-24 04:55:35	ID requested
1	2024-05-22 01:10:37	announced
⏵ 2	2024-10-22 06:40:50	announced	2024-10-22: Updated project metadata.

10.1038/s41420-024-01913-8;

Kliza KW, Song W, Pinzuti I, Schaubeck S, Kunzelmann S, Kuntin D, Fornili A, Pandini A, Hofmann K, Garnett JA, Stieglitz B, Husnjak K, N4BP1 functions as a dimerization-dependent linear ubiquitin reader which regulates TNF signalling. Cell Death Discov, 10(1):183(2024) [pubmed]

submitter keyword: Caspase 8, proteolytic processing,N4BP1

Dr Koraljka Husnjak
contact affiliation	Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
contact email	k.husnjak@biochem2.uni-frankfurt.de
lab head
Katarzyna Kliza
contact affiliation	Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen
contact email	kkliza@science.ru.nl
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/2024/05/PXD024355

PRIDE project URI

• PRIDE
  1. PXD024355
     1. Label: PRIDE project
     2. Name: N4BP1 is a unique, dimerization-dependent linear ubiquitin reader that regulates TNFR1 signalling through linear ubiquitin binding and Caspase-8-dependent processing