ArticleThe Journal of biological chemistry2011
Syk activation of phosphatidylinositol 3-kinase/Akt prevents HtrA2-dependent loss of X-linked inhibitor of apoptosis protein (XIAP) to promote survival of Epstein-Barr virus+ (EBV+) B cell lymphomas.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Epstein-Barr virus receptors: classification, functional mechanisms, and pathogenic implications.Journal of virology · 2026Review
- A single mycobacterial ligand organizes multi-receptor signaling to reprogram macrophage lipid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Triple Latency as a Driver of Chronic Inflammation: An Integrative View of HSV, EBV, and CMV Persistence in Immunocompetent Hosts.Clinics and practice · 2026Review
- Regulation mechanism of EBV-encoded EBER1 and LMP2A on YAP1 and the impact of YAP1 on the EBV infection status in EBV-associated gastric carcinoma.Virus research · 2024Article
- Signaling pathways of EBV-induced oncogenesis.Cancer cell international · 2021Review
- Article
- Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Epstein-Barr Virus Latent Membrane Protein 1 Regulates Host B Cell MicroRNA-155 and Its Target FOXO3aFrontiers in microbiology · 2019Article
- The complex of TRIP-Br1 and XIAP ubiquitinates and degrades multiple adenylyl cyclase isoforms.eLife · 2017Article
- Article
- Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency.Frontiers in immunology · 2017Review
- Article
- Microenvironment abnormalities and lymphomagenesis: Immunological aspects.Seminars in cancer biology · 2015Review
- MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer.Cell death & disease · 2015Article
- Review
- Pathogen manipulation of B cells: the best defence is a good offence.Nature reviews. Microbiology · 2015Review
- Calling in SYK: SYK's dual role as a tumor promoter and tumor suppressor in cancer.Biochimica et biophysica acta · 2015Review
- Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes.PLoS neglected tropical diseases · 2014Article
- Getting Syk: spleen tyrosine kinase as a therapeutic target.Trends in pharmacological sciences · 2014Review
- The interplay between Epstein-Barr virus and B lymphocytes: implications for infection, immunity, and disease.Immunologic research · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
B cell lymphoma survival requires tonic or ligand-independent signals through activation of Syk by the B cell receptor. The Epstein-Barr virus (EBV) protein latent membrane 2a (LMP2a), a mimic of the B cell receptor, provides constitutive survival signals for latently infected cells through Syk activation; however, the precise downstream mechanisms coordinating this survival response in EBV+ B cell lymphomas remain to be elucidated. Herein, we assess the mechanism of Syk survival signaling in EBV+ B cell lymphomas from post-transplant lymphoproliferative disorder (PTLD) to discover virally controlled therapeutic targets involved in lymphomagenesis and tumor progression. Using small molecule inhibition and siRNA strategies, we show that Syk inhibition reduces proliferation and induces apoptosis of PTLD-derived EBV+ B cell lines. Syk inhibition also reduces autocrine IL-10 production. Although Syk inhibition attenuates signaling through both the PI3K/Akt and Erk pathways, only PI3K/Akt inhibition causes apoptosis of PTLD-derived cell lines. Loss of the endogenous caspase inhibitor XIAP is observed after Syk or PI3K/Akt inhibition. The loss of XIAP and apoptosis that results from Syk or PI3K/Akt inhibition is reversed by inhibition of the mitochondrial protease HtrA2. Thus, Syk drives EBV+ B cell lymphoma survival through PI3K/Akt activation, which prevents the HtrA2-dependent loss of XIAP. Syk, Akt, and XIAP antagonists may present potential new therapeutic strategies for PTLD through targeting of EBV-driven survival signals.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.