PXD018566-1

PXD018566 is an original dataset announced via ProteomeXchange.

Title	Rewiring of B cell receptor signaling by Epstein-Barr virus LMP2A
Description	Epstein-Barr virus (EBV) infects human B cells and reprograms them to allow virus replication and persistence. One key viral factor in this process is latent membrane protein 2A (LMP2A), which has been described as a B cell receptor (BCR) mimic promoting malignant transformation. However, how LMP2A signaling contributes to tumorigenesis remains elusive. By systematically comparing LMP2A and BCR signaling using quantitative phosphoproteomics and transcriptome profiling, we identified molecular mechanisms through which LMP2A affects B cell biology. Consistent with previous literature, we found that LMP2A mimics a subset of BCR signaling events, including tyrosine-phosphorylation of the kinase SYK, the calcium initiation complex consisting of BLNK, BTK, PLC2, and its downstream transcription factor NFAT. However, the vast majority of LMP2A-induced signaling events markedly differed from those induced by BCR stimulation. These included differential phosphorylation of kinases, phosphatases, adaptor proteins, transcription factors such as NFB and TCF3, as well as widespread changes in the transcriptional output of LMP2A-expressing B cells. LMP2A affected apoptosis and cell cycle checkpoints by dysregulating the expression of apoptosis regulators such as Bcl-xL and the tumor suppressor retinoblastoma-associated protein (RB1). Accordingly, LMP2A cooperated with drivers of Burkitt lymphoma, overexpressed MYC and an oncogenic cyclin D3 mutant, by counteracting the pro-apoptotic effects of MYC and by further inhibiting RB1 function to promote cell growth. Our results indicate that LMP2A rewires rather than mimics BCR signaling, promoting a signaling output that predisposes EBV-infected B cells to hyperproliferation and eventual malignant transformation.
HostingRepository	PRIDE
AnnounceDate	2020-09-22
AnnouncementXML	Submission_2020-09-22_05:23:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanlong Ji
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-15 01:12:52	ID requested
⏵ 1	2020-09-22 05:23:11	announced

Dataset with its publication pending

submitter keyword: Signal transduction, lymphoma, B cell receptor, Epstein-Barr virus

Thomas Oellerich
contact affiliation	Department of Medicine II, Hematology/Oncology, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
contact email	thomas.oellerich@kgu.de
lab head
Yanlong Ji
contact affiliation	Max-Planck-Institute for Biophysical Chemistry
contact email	yanlong.ji@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018566
     1. Label: PRIDE project
     2. Name: Rewiring of B cell receptor signaling by Epstein-Barr virus LMP2A