ArticleMolecular and cellular biology2000
The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and -independent pathways: roles for phosphatidylinositol 3-kinase and Raf.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 187 citations in OpenAlex.
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- BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia.Pharmaceutics · 2022Review
- Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring T315I mutant.Cell death & disease · 2018Article
- Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy.Molecular diagnosis & therapy · 2016Review
- High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia.Leukemia · 2016Article
- Chronic myeloid leukemia: reminiscences and dreams.Haematologica · 2016Review
- Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia.Journal of translational medicine · 2016Article
- Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.Frontiers in oncology · 2015Review
- SAHA and S116836, a novel tyrosine kinase inhibitor, synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells.Cancer biology & therapy · 2014Article
- Kinase-independent mechanisms of resistance of leukemia stem cells to tyrosine kinase inhibitors.Stem cells translational medicine · 2014Review
- S-adenosylmethionine limitation induces p38 mitogen-activated protein kinase and triggers cell cycle arrest in G1.Journal of cell science · 2014Article
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- Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells.Protein & cell · 2013Review
- SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation.BMC cancer · 2013Article
- The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells.Journal of assisted reproduction and genetics · 2012Article
- The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias.Advances in hematology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Bcr-Abl tyrosine kinase constitutively activates cytokine signal transduction pathways that stimulate growth and prevent apoptosis in hematopoietic cells. The antiapoptotic action of interleukin-3 (IL-3) has been linked to a signaling pathway which inactivates the proapoptotic protein Bad by phosphorylation through kinases such as Akt and Raf. Here we report also that expression of Bcr-Abl leads to phosphorylation of Bad in hematopoietic cells. Bad phosphorylation induced by Bcr-Abl is kinase dependent, requires phosphatidylinositol 3-kinase (PI3-kinase), and mitochondrial targeting of Raf, and occurs independently of Erk. The ability of Bcr-Abl to confer cytokine-independent survival to hematopoietic cells was compromised by inhibitors of PI3-kinase, as well as by a dominant negative form of Raf targeted to the mitochondria. Furthermore, when the capacity of Bcr-Abl to phosphorylate Bad was completely blocked by dominant negative Raf, a subpopulation of cells remained viable, providing evidence for Bad-independent survival pathways. This alternative survival pathway remained PI3-kinase dependent. Finally, Bcr-Abl, but not IL-3, inhibited the proapoptotic activity of overexpressed Bad. We conclude that the antiapoptotic function of Bcr-Abl is mediated through pathways involving PI3-kinase and Raf and that survival can occur in the absence of Bad phosphorylation.
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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.