ArticlePharmaceutical research2012
Changing the subcellular location of the oncoprotein Bcr-Abl using rationally designed capture motifs.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells.Cell research · 2024Article
- Article
- Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.PloS one · 2015Article
- MAPK15 mediates BCR-ABL1-induced autophagy and regulates oncogene-dependent cell proliferation and tumor formation.Autophagy · 2015Article
- Multidomain targeting of Bcr-Abl by disruption of oligomerization and tyrosine kinase inhibition: toward eradication of CML.Molecular pharmaceutics · 2013Article
- Enhanced and selective killing of chronic myelogenous leukemia cells with an engineered BCR-ABL binding protein and imatinib.Molecular pharmaceutics · 2012Article
- Selective targeting of c-Abl via a cryptic mitochondrial targeting signal activated by cellular redox status in leukemic and breast cancer cells.Pharmaceutical research · 2012Article
- New insights and clinical advancements in cellular oncology.Cellular oncology (Dordrecht, Netherlands) · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeBcr-Abl, the causative agent of chronic myelogenous leukemia (CML), localizes in the cytoplasm where its oncogenic signaling leads to proliferation of cells. If forced into the nucleus Bcr-Abl causes apoptosis. To achieve nuclear translocation, binding domains for capture of Bcr-Abl were generated and attached to proteins with signals destined for the nucleus. These resulting proteins would be capable of binding and translocating endogenous Bcr-Abl to the nucleus.
methodsBcr-Abl was targeted at 3 distinct domains for capture: by construction of high affinity intracellular antibody domains (iDabs) to regions of Bcr-Abl known to promote cytoplasmic retention, via its coiled coil domain (CC), and through a naturally occurring protein-protein interaction domain (RIN1). These binding domains were then tested for their ability to escort Bcr-Abl into the nucleus using a "protein switch" or attachment of 4 nuclear localization signals (NLSs).
resultsAlthough RIN1, ABI7-iDab, and CCmut3 constructs all produced similar colocalization with Bcr-Abl, only 4NLS-CCmut3 produced efficient nuclear translocation of Bcr-Abl.
conclusionsWe demonstrate that a small binding domain can be used to control the subcellular localization of Bcr-Abl, which may have implications for CML therapy. Our ultimate future goal is to change the location of critical proteins to alter their function.
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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.