ArticleProceedings of the National Academy of Sciences of the United States of America2009
Charting the molecular network of the drug target Bcr-Abl.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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
82 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.International journal of molecular sciences · 2024Pooled it
- Article
- Targeting ABL Tyrosine Kinase in Chronic Myeloid Leukemia: Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Thiazolone Derivatives.Pharmaceutics · 2026Article
- Multimodal gene and targeted drug therapy for chronic myelogenous leukemia using BIM/MCL-1 chimeric nanoparticle: computational target analysis and therapeutic validation.Nano convergence · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Article
- Synergistic effect of asciminib with reduced doses of ponatinib in human Ph + myeloid leukemia with the T315M mutation.International journal of hematology · 2025Article
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- STS-1 and STS-2, Multi-Enzyme Proteins Equipped to Mediate Protein-Protein Interactions.International journal of molecular sciences · 2023Review
- USP15 regulates p66Shc stability associated with Drp1 activation in liver ischemia/reperfusion.Cell death & disease · 2022Article
- circCRKL, a circRNA derived from CRKL, regulates BCR-ABL via sponging miR-877-5p to promote chronic myeloid leukemia cell proliferation.Journal of translational medicine · 2022Article
- BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia.Pharmaceutics · 2022Review
- Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia.Cancers · 2021Review
- Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics.Nature communications · 2021Article
- Dynamin 3 Inhibits the Proliferation of Non-small-Cell Lung Cancer Cells by Suppressing c-MET-GBR2-STAT3 Complex Formation.Frontiers in cell and developmental biology · 2021Article
- Regulation of Beclin 1-Mediated Autophagy by Oncogenic Tyrosine Kinases.International journal of molecular sciences · 2020Review
- Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex.Cellular and molecular life sciences : CMLS · 2020Article
- Article
- Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
The tyrosine kinase Bcr-Abl causes chronic myeloid leukemia and is the cognate target of tyrosine kinase inhibitors like imatinib. We have charted the protein-protein interaction network of Bcr-Abl by a 2-pronged approach. Using a monoclonal antibody we have first purified endogenous Bcr-Abl protein complexes from the CML K562 cell line and characterized the set of most tightly-associated interactors by MS. Nine interactors were subsequently subjected to tandem affinity purifications/MS analysis to obtain a molecular interaction network of some hundred cellular proteins. The resulting network revealed a high degree of interconnection of 7 "core" components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2), and their links to different signaling pathways. Quantitative proteomics analysis showed that tyrosine kinase inhibitors lead to a disruption of this network. Certain components still appear to interact with Bcr-Abl in a phosphotyrosine-independent manner. We propose that Bcr-Abl and other drug targets, rather than being considered as single polypeptides, can be considered as complex protein assemblies that remodel upon drug action.
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.