ArticlePLoS biology2007
DNA damage-induced Bcl-xL deamidation is mediated by NHE-1 antiport regulated intracellular pH.
Article in PLoS biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 115 citations in OpenAlex.
- Neutrophil Death in Myeloproliferative Neoplasms: Shedding More Light on Neutrophils as a Pathogenic Link to Chronic Inflammation.International journal of molecular sciences · 2022Review
- Inhibition of c-MYC-miRNA 19 Pathway Sensitized CML K562 Cells to Etoposide via NHE1 Upregulation.Oxidative medicine and cellular longevity · 2022Article
- Conformational States of the Cytoprotective Protein Bcl-xL.Biophysical journal · 2020Article
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- Regulation of apoptosis by an intrinsically disordered region of Bcl-xL.Nature chemical biology · 2018Article
- GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells.Cancer letters · 2017Article
- Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation.BMB reports · 2016Article
- Recombinant human heterodimeric IL-15 complex displays extensive and reproducible N- and O-linked glycosylation.Glycoconjugate journal · 2016Article
- JAK2V617F mediates resistance to DNA damage-induced apoptosis by modulating FOXO3A localization and Bcl-xL deamidation.Oncogene · 2016Article
- N52 monodeamidated Bcl‑xL shows impaired oncogenic properties in vivo and in vitro.Oncotarget · 2016Article
- Article
- Mitochondrial and postmitochondrial survival signaling in cancer.Mitochondrion · 2014Review
- Structure-based prediction of asparagine and aspartate degradation sites in antibody variable regions.PloS one · 2014Article
- Getting away with murder: how does the BCL-2 family of proteins kill with immunity?Annals of the New York Academy of Sciences · 2013Review
- Control of cellular Bcl-xL levels by deamidation-regulated degradation.PLoS biology · 2013Article
- JAK2 and genomic instability in the myeloproliferative neoplasms: a case of the chicken or the egg?American journal of hematology · 2012Review
- Protein L-isoaspartyl methyltransferase regulates p53 activity.Nature communications · 2012Article
- The microRNA 15a/16-1 cluster down-regulates protein repair isoaspartyl methyltransferase in hepatoma cells: implications for apoptosis regulation.The Journal of biological chemistry · 2011Article
- Dysregulated pH: a perfect storm for cancer progression.Nature reviews. Cancer · 2011Review
- Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pro-survival protein Bcl-xL is critical for the resistance of tumour cells to DNA damage. We have previously demonstrated, using a mouse cancer model, that oncogenic tyrosine kinase inhibition of DNA damage-induced Bcl-xL deamidation tightly correlates with T cell transformation in vivo, although the pathway to Bcl-xL deamidation remains unknown and its functional consequences unclear. We show here that rBcl-xL deamidation generates an iso-Asp(52)/iso-Asp(66) species that is unable to sequester pro-apoptotic BH3-only proteins such as Bim and Puma. DNA damage in thymocytes results in increased expression of the NHE-1 Na/H antiport, an event both necessary and sufficient for subsequent intracellular alkalinisation, Bcl-xL deamidation, and apoptosis. In murine thymocytes and tumour cells expressing an oncogenic tyrosine kinase, this DNA damage-induced cascade is blocked. Enforced intracellular alkalinisation mimics the effects of DNA damage in murine tumour cells and human B-lineage chronic lymphocytic leukaemia cells, thereby causing Bcl-xL deamidation and increased apoptosis. Our results define a signalling pathway leading from DNA damage to up-regulation of the NHE-1 antiport, to intracellular alkalanisation to Bcl-xL deamidation, to apoptosis, representing the first example, to our knowledge, of how deamidation of internal asparagine residues can be regulated in a protein in vivo. Our findings also suggest novel approaches to cancer 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.