ArticleOncotarget2014
The anti-apoptotic form of tyrosine kinase Lyn that is generated by proteolysis is degraded by the N-end rule pathway.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- An Enigma of N-termini dependent protein degradation.Biochemistry and biophysics reports · 2025Article
- Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair.EMBO reports · 2022Article
- Regulation of Neurodegeneration-associated Protein Fragments by the N-degron Pathways.Neurotoxicity research · 2022Review
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- The ATF3 Transcription Factor Is a Short-Lived Substrate of the Arg/N-Degron Pathway.Biochemistry · 2020Article
- N-degron-mediated degradation and regulation of mitochondrial PINK1 kinase.Current genetics · 2020Review
- The Arg/N-Degron Pathway-A Potential Running Back in Fine-Tuning the Inflammatory Response?Biomolecules · 2020Article
- Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Investigating age‑induced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis.Molecular medicine reports · 2019Article
- Protective autophagy or autophagic death: effects of BEZ235 on chronic myelogenous leukemia.Cancer management and research · 2019Article
- Regulating Apoptosis by Degradation: The N-End Rule-Mediated Regulation of Apoptotic Proteolytic Fragments in Mammalian Cells.International journal of molecular sciences · 2018Review
- Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA.Molecules (Basel, Switzerland) · 2017Article
- The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites.Molecules (Basel, Switzerland) · 2017Review
- Spectroscopic Studies on the Molecular Ageing of Serum Albumin.Molecules (Basel, Switzerland) · 2016Article
- The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19).Molecules (Basel, Switzerland) · 2016Article
- A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells.International journal of molecular sciences · 2016Article
- Phosphorylation Impacts N-end Rule Degradation of the Proteolytically Activated Form of BMX Kinase.The Journal of biological chemistry · 2016Article
- Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.Molecules (Basel, Switzerland) · 2016Article
- Analyzing N-terminal Arginylation through the Use of Peptide Arrays and Degradation Assays.The Journal of biological chemistry · 2016Article
- Posttranslational arginylation enzyme Ate1 affects DNA mutagenesis by regulating stress response.Cell death & disease · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of apoptotic pathways results in the caspase cleavage of the Lyn tyrosine kinase to generate the N-terminal truncated LynΔN. This LynΔN fragment has been demonstrated to exert negative feedback on imatinib induced apoptosis in chronic myelogenous leukemia (CML) K562 cells. Our investigations focus on LynΔN stability and how reduced stability reduces imatinib resistance. As the proteolytical generated LynΔN has a leucine as an N-terminal amino acid, we hypothesized that LynΔN would be degraded by the N-end rule pathway. We demonstrated that LynΔN is unstable and that its stability is dependent on the identity of its N-terminus. Additionally we established that LynΔN degradation could be inhibited by inhibiting either the proteasome or knocking down the UBR1 and UBR2 ubiquitin E3 ligases. Importantly, we also demonstrate that LynΔN degradation by the N-end rule counters the imatinib resistance of K562 cells provided by LynΔN expression. Together our data suggest a possible mechanism for the N-end rule pathway having a link to imatinib resistance in CML. With LynΔN being an N-end rule substrate, it provides the first example that this pathway can also provide a pro-apoptotic function as previous reports have currently only demonstrated anti-apoptotic roles for the N-end rule pathway.
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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.