ArticleMolecular pharmaceutics2012
Improved coiled-coil design enhances interaction with Bcr-Abl and induces apoptosis.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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
18 citing papers in PubMed.
- Phase separation drives the innate sluggishness of BCR-ABL1 in response to targeted therapy.Cell research · 2026Article
- Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML.The journal of physical chemistry. B · 2024Article
- Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells.Cell research · 2024Article
- Computational Modeling of Stapled Coiled-Coil Inhibitors Against Bcr-Abl: Toward a Treatment Strategy for CML.bioRxiv : the preprint server for biology · 2023Article
- Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire.Protein science : a publication of the Protein Society · 2023Article
- Review
- A coiled-coil mimetic intercepts BCR-ABL1 dimerization in native and kinase-mutant chronic myeloid leukemia.Leukemia · 2015Article
- Re-engineered p53 chimera with enhanced homo-oligomerization that maintains tumor suppressor activity.Molecular pharmaceutics · 2014Article
- Cell-penetrating fusion peptides OD1 and OD2 interact with Bcr-Abl and influence the growth and apoptosis of K562 cells.Molecular and cellular biochemistry · 2014Article
- Resistant mutations in CML and Ph(+)ALL - role of ponatinib.Biologics : targets & therapy · 2014Review
- The DNA binding domain of p53 is sufficient to trigger a potent apoptotic response at the mitochondria.Molecular pharmaceutics · 2013Article
- Multidomain targeting of Bcr-Abl by disruption of oligomerization and tyrosine kinase inhibition: toward eradication of CML.Molecular pharmaceutics · 2013Article
- A single mutant, A276S of p53, turns the switch to apoptosis.Molecular pharmaceutics · 2013Article
- Disrupting BCR-ABL in combination with secondary leukemia-specific pathways in CML cells leads to enhanced apoptosis and decreased proliferation.Molecular pharmaceutics · 2013Article
- Utilizing the estrogen receptor ligand-binding domain for controlled protein translocation to the insoluble fraction.Pharmaceutical research · 2012Article
- 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
- Direct induction of apoptosis using an optimal mitochondrially targeted p53.Molecular pharmaceutics · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
The oncoprotein Bcr-Abl drives aberrant downstream activity through trans-autophosphorylation of homo-oligomers in chronic myelogenous leukemia (CML).(1, 2) The formation of Bcr-Abl oligomers is achieved through the coiled-coil domain at the N-terminus of Bcr.(3, 4) We have previously reported a modified version of this coiled-coil domain, CCmut2, which exhibits disruption of Bcr-Abl oligomeric complexes and results in decreased proliferation of CML cells and induction of apoptosis.(5) A major contributing factor to these enhanced capabilities is the destabilization of the CCmut2 homodimers, increasing the availability to interact with and inhibit Bcr-Abl. Here, we included an additional mutation (K39E) that could in turn further destabilize the mutant homodimer. Incorporation of this modification into CCmut2 (C38A, S41R, L45D, E48R, Q60E) generated what we termed CCmut3, and resulted in further improvements in the binding properties with the wild-type coiled-coil domain representative of Bcr-Abl [corrected]. A separate construct containing one revert mutation, CCmut4, did not demonstrate improved oligomeric properties and indicated the importance of the L45D mutation. CCmut3 demonstrated improved oligomerization via a two-hybrid assay as well as through colocalization studies, in addition to showing similar biologic activity as CCmut2. The improved binding between CCmut3 and the Bcr-Abl coiled-coil may be used to redirect Bcr-Abl to alternative subcellular locations with interesting therapeutic implications.
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.