ArticleCell death and differentiation2009
TGF-beta induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL.
Article in Cell death and differentiation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
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- Busulfan Chemotherapy Downregulates TAF7/TNF-α Signaling in Male Germ Cell Dysfunction.Biomedicines · 2024Article
- Recent development of oral vaccines (Review).Experimental and therapeutic medicine · 2024Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Aerobic training and vitamin E administration ameliorates cardiac apoptosis markers in rats exposed to methamphetamine.European journal of translational myology · 2023Article
- The role of transforming growth factor beta in thyroid autoimmunity: current knowledge and future perspectives.Reviews in endocrine & metabolic disorders · 2022Review
- Article
- Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma.Cancers · 2022Review
- New perspectives on the regulation of germinal center reactionFrontiers in immunology · 2022Review
- RGS5-TGFβ-Smad2/3 axis switches pro- to anti-apoptotic signaling in tumor-residing pericytes, assisting tumor growth.Cell death and differentiation · 2021Article
- Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC.Biomedicines · 2021Review
- Knockdown of long non‑coding RNA ANRIL inhibits the proliferation and promotes the apoptosis of Burkitt lymphoma cells through the TGF‑β1 signaling pathway.Molecular medicine reports · 2021Article
- Long-TermMicroorganisms · 2020Article
- Klotho and the Treatment of Human Malignancies.Cancers · 2020Review
- BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer.Cell death & disease · 2020Article
- Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.Cell death & disease · 2020Article
- Positive and negative cooperativity of TNF and Interferon-γ in regulating synovial fibroblast function and B cell survival in fibroblast/B cell co-cultures.Scientific reports · 2020Article
- Therapeutic Targets for the Treatment of Cardiac Fibrosis and Cancer: Focusing on TGF-β Signaling.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Transforming growth factor-beta (TGF-beta) potently induces apoptosis in Burkitt's lymphoma (BL) cell lines and in explanted primary human B lymphocytes. The physiological relevance and mechanism of TGF-beta-mediated apoptosis induction in these cells remains to be determined. Here we demonstrate the requirement for TGF-beta-mediated regulation of BIK and BCL-X(L) to activate an intrinsic apoptotic pathway in centroblastic BL cells. TGF-beta directly induced transcription of BIK and a consensus Smad-binding element identified in the BIK promoter recruits TGF-beta-activated Smad transcription factor complexes in vivo. TGF-beta also transcriptionally repressed expression of the apoptosis inhibitor BCL-X(L). Inhibition of BCL-X(L) sensitised BL cells to TGF-beta-induced apoptosis whereas overexpression of BCL-X(L) or suppression of BIK by shRNA, diminished TGF-beta-induced apoptosis. BIK and BCL-X(L) were also identified as TGF-beta target genes in purified normal human centroblast B cells and immunohistochemical analyses of tonsil tissue revealed widespread TGF-beta receptor-regulated Smad activation and a focal pattern of BIK expression. Furthermore, using a selective inhibitor of the TGF-beta receptor we provide evidence that autocrine TGF-beta signalling through ALK5 contributes to the default apoptotic programme in normal human centroblasts undergoing spontaneous apoptosis. Our data suggests that TGF-beta may act as a physiological mediator of human germinal centre homoeostasis by regulation of BIK and BCL-X(L).
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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.