PXD017601

PXD017601 is an original dataset announced via ProteomeXchange.

Title	Non-apoptotic Fas signaling controls CD40 dependent mTOR activation and human B cell fate via PTEN nuclear exclusion
Description	Defective Fas signaling causes autoimmune lymphoproliferative syndrome (ALPS). While defective apoptosis may impair negative selection and removal of autoreactive B lymphocytes, Fas transmits also non-apoptotic signals. We show herethat transient Fas ligation in CD40L-stimulated human B cells specifically decreased the mTOR axis activation without causing apoptosis. This signal modulation was absent in ALPS patients. Rather, mTOR signaling was enhanced in germinal center (GC) B cells and plasmablasts derived from a ALPS patient lymph node . Mechanistically, transient Fas engagement induced recruitment of DAXX to the activated Fas complex and nuclear exclusion of PTEN. Likewise, Fas stimulation promoted expression of transcripts like MYC and CXCR4, that regulate GC formation and fate decisions of established GC B cells. We suggest that non-apoptotic Fas signaling has a physiological impact on activated B cell fate decisions explaining the effectiveness of mTOR inhibitors in the treatment of ALPS autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2024-04-08
AnnouncementXML	Submission_2024-04-08_02:47:38.782.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Rizzi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-19 00:35:13	ID requested
⏵ 1	2024-04-08 02:47:39	announced

10.1126/SCIIMMUNOL.ADJ5948;

submitter keyword: Fas signaling, mTOR activation, B cells, subcellular fractionation

Marta Rizzi
contact affiliation	Clinic for Rheumatology and Clinical Immunology University of Freiburg Germany
contact email	marta.rizzi@uniklinik-freiburg.de
lab head
Marta Rizzi
contact affiliation	Clinic for Rheumatology and Clinical Immunology University of Freiburg
contact email	marta.rizzi@uniklinik-freiburg.de
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/2024/04/PXD017601

PRIDE project URI

• PRIDE
  1. PXD017601
     1. Label: PRIDE project
     2. Name: Non-apoptotic Fas signaling controls CD40 dependent mTOR activation and human B cell fate via PTEN nuclear exclusion