ArticleLeukemia2011
ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- The molecular signature ofiScience · 2024Article
- Development of anMolecular therapy. Methods & clinical development · 2023Article
- Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats.Brain and behavior · 2020Article
- A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia.Molecular cytogenetics · 2016Article
- Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.PloS one · 2015Article
- The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.Traffic (Copenhagen, Denmark) · 2014Article
- RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to determine the fate of EGFR.Journal of cell science · 2012Article
- RIN1 exhibits oncogenic property to suppress apoptosis and its aberrant accumulation associates with poor prognosis in melanoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
- Changing the subcellular location of the oncoprotein Bcr-Abl using rationally designed capture motifs.Pharmaceutical research · 2012Article
- Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted therapies.Journal of cellular and molecular medicine · 2012Review
- Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling.Science signaling · 2011Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
ABL gene translocations create constitutively active tyrosine kinases that are causative in chronic myeloid leukemia, acute lymphocytic leukemia and other hematopoietic malignancies. Consistent retention of ABL SH3/SH2 autoinhibitory domains, however, suggests that these leukemogenic tyrosine kinase fusion proteins remain subject to regulation. We resolve this paradox, demonstrating that BCR-ABL1 kinase activity is regulated by RIN1, an ABL SH3/SH2 binding protein. BCR-ABL1 activity was increased by RIN1 overexpression and decreased by RIN1 silencing. Moreover, Rin1(-/-) bone marrow cells were not transformed by BCR-ABL1, ETV6-ABL1 or BCR-ABL1(T315I), a patient-derived drug-resistant mutant, as judged by growth factor independence. Rescue by ectopic RIN1 verified a cell autonomous mechanism of collaboration with BCR-ABL1 during transformation. Sensitivity to the ABL kinase inhibitor imatinib was increased by RIN1 silencing, consistent with RIN1 stabilization of an activated BCR-ABL1 conformation having reduced drug affinity. The dependence on activation by RIN1 to unleash full catalytic and cell transformation potential reveals a previously unknown vulnerability that could be exploited for treatment of leukemic cases driven by ABL translocations. The findings suggest that RIN1 targeting could be efficacious for imatinib-resistant disease and might complement ABL kinase inhibitors in first-line therapy.
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