The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells
| Autor: | Richard Monni, Fabrice Gouilleux, Roland Berger, Jacques Ghysdael, M. Mauchauffe, Virginie Penard-Lacronique, Sylvie Gisselbrecht, Susana Constantino Rosa Santos, Olivier Bernard |
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| Přispěvatelé: | Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Laboratoire d'Oncologie cellulaire et moléculaire (Inserm U363), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Régulations cellulaires et oncogenèse (RCO), Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut Cochin de Génétique Moléculaire [Paris] (CNRS UPR 0415 - ICGM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Gouilleux, Fabrice, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
Cancer Research Oncogene Proteins Fusion Suppressor of Cytokine Signaling Proteins Ba/F3 Mice 0302 clinical medicine hemic and lymphatic diseases SOCS5 SOCS6 SOCS3 Cells Cultured Cell Line Transformed Receptors Interferon B-Lymphocytes 0303 health sciences Janus kinase 1 Gene Expression Regulation Leukemic [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Protein-Tyrosine Kinases TEL-JAK2 Cell biology Cysteine Endopeptidases 030220 oncology & carcinogenesis TEL-Jak2 [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Cytokines interferon-gamma Signal transduction Protein Binding Signal Transduction Proteasome Endopeptidase Complex [SDV.CAN]Life Sciences [q-bio]/Cancer Biology leukemogenesis 03 medical and health sciences Suppressor of Cytokine Signaling 1 Protein [SDV.CAN] Life Sciences [q-bio]/Cancer Multienzyme Complexes Proto-Oncogene Proteins [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Genetics Animals Ubiquitins Molecular Biology 030304 developmental biology Suppressor of cytokine signaling 1 Janus Kinase 2 Hematopoietic Stem Cells Socs1 Repressor Proteins Cancer research Carrier Proteins Janus kinase |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2001, 20 (7), pp.849-858. ⟨10.1038/sj.onc.1204201⟩ Oncogene, 2001, 20 (7), pp.849-858. ⟨10.1038/sj.onc.1204201⟩ |
| ISSN: | 0950-9232 1476-5594 |
| Popis: | International audience; The leukemia-associated TEL-Jak2 fusion protein possesses a constitutive tyrosine kinase activity and transforming properties in hematopoietic cell lines and animal models. In the murine pro-B Ba/F3 cell line, this fusion constitutively activates the Signal Transducer and Activator of Transcription 5 (Stat5) factors and, as a consequence, induces the sustained expression of various Stat5-target genes including the Cytokine Inducible SH2-containing protein (Cis) gene, which codes for a member of the Suppressor of Cytokine Signaling (Socs) protein family. In TEL-Jak2-transformed Ba/F3 cells, we also observed the upregulation of the Socs1 gene, whose product has been reported to negatively regulate the Jak kinase activity. In transient transfection experiments, Socs1 physically interacts with TEL-Jak2 and interferes with the TEL-Jak2-induced phosphorylation and activation of Stat5 factors, probably through the Socs1-induced proteasome-mediated degradation of the fusion protein. Interestingly, TEL-Jak2-expressing Ba/F3 cells were found to be resistant to the anti-proliferative activities of gamma interferon (IFN-gamma) seemingly as a consequence of Socs1 constitutive expression. These results indicate that the Socs1-dependent cytokine feedback loop, although active, is bypassed by the TEL-Jak2 fusion, but may play a role in the leukemogenic process by altering the cytokine responses of the leukemic cells. Our results also suggest that Socs1 plays a role in shutting down the signaling from the normally activated Jak2 kinase by inducing its proteasome-dependent degradation. |
| Databáze: | OpenAIRE |
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