ArticleBlood2010
Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Towards a Better Understanding of the Relationships between Galectin-7, p53 and MMP-9 during Cancer Progression.Biomolecules · 2021Review
- A redox switch regulates the structure and function of anti-apoptotic BFL-1.Nature structural & molecular biology · 2020Article
- Identification of a Covalent Molecular Inhibitor of Anti-apoptotic BFL-1 by Disulfide Tethering.Cell chemical biology · 2020Article
- BFL1 modulates apoptosis at the membrane level through a bifunctional and multimodal mechanism showing key differences with BCLXL.Cell death and differentiation · 2019Article
- TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1.Cell death and differentiation · 2019Article
- Precision Targeting of BFL-1/A1 and an ATM Co-dependency in Human Cancer.Cell reports · 2018Article
- Article
- Differential effects of Vav-promoter-driven overexpression of BCLX and BFL1 on lymphocyte survival and B cell lymphomagenesis.The FEBS journal · 2018Article
- Perturbing mitosis for anti-cancer therapy: is cell death the only answer?EMBO reports · 2018Review
- Crystal Structures of Anti-apoptotic BFL-1 and Its Complex with a Covalent Stapled Peptide Inhibitor.Structure (London, England : 1993) · 2018Article
- Article
- MYC selects against reduced BCL2A1/A1 protein expression during B cell lymphomagenesis.Oncogene · 2017Article
- Selective Covalent Targeting of Anti-Apoptotic BFL-1 by Cysteine-Reactive Stapled Peptide Inhibitors.Cell chemical biology · 2016Article
- Polyubiquitination and proteasomal turnover controls the anti-apoptotic activity of Bcl-B.Oncogene · 2013Article
- Alzheimer's disease risk factor lymphocyte-specific protein tyrosine kinase regulates long-term synaptic strengthening, spatial learning and memory.Cellular and molecular life sciences : CMLS · 2013Article
- Regulation of A1 by OX40 contributes to CD8(+) T cell survival and anti-tumor activity.PloS one · 2013Article
- Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B.Cell death & disease · 2012Article
- A1/Bfl-1 in leukocyte development and cell death.Experimental cell research · 2012Review
- Targeting antiapoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in leukocyte development in mice.Blood · 2012Article
- BCL2A1: the underdog in the BCL2 family.Cell death and differentiation · 2012Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The antiapoptotic Bcl-2 family member Bfl-1 is up-regulated in many human tumors in which nuclear factor-kappaB (NF-kappaB) is implicated and contributes significantly to tumor cell survival and chemoresistance. We previously found that NF-kappaB induces transcription of bfl-1 and that the Bfl-1 protein is also regulated by ubiquitin-mediated proteasomal degradation. However, the role that dysregulation of Bfl-1 turnover plays in cancer is not known. Here we show that ubiquitination-resistant mutants of Bfl-1 display increased stability and greatly accelerated tumor formation in a mouse model of leukemia/lymphoma. We also show that tyrosine kinase Lck is up-regulated and activated in these tumors and leads to activation of the IkappaB kinase, Akt, and extracellular signal-regulated protein kinase signaling pathways, which are key mediators in cancer. Coexpression of Bfl-1 and constitutively active Lck promoted tumor formation, whereas Lck knockdown in tumor-derived cells suppressed leukemia/lymphomagenesis. These data demonstrate that ubiquitination is a critical tumor suppression mechanism regulating Bfl-1 function and suggest that mutations in bfl-1 or in the signaling pathways that control its ubiquitination may predispose one to cancer. Furthermore, because bfl-1 is up-regulated in many human hematopoietic tumors, this finding suggests that strategies to promote Bfl-1 ubiquitination may improve therapy.
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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.