| Murine embryonic fibroblasts lacking TC-PTP display delayed G1 phase through defective NF-kappaB activation. | |
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MedLine Citation:
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PMID: 11498795 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous results suggested a potential role for T-cell protein tyrosine phosphatase (TC-PTP) in cell proliferation. However, no conclusive data has supported such a function in the modulation of this process. In order to clarify this issue, we isolated TC-PTP-/- murine embryonic fibroblasts (MEFs) as well as cell lines to characterize the role of TC-PTP in the control of cell proliferation and cell cycle. Both TC-PTP-/- primary MEFs and cell lines proliferate slower than TC-PTP+/+ cells. We also demonstrated that TC-PTP-/- cells have a slow progression through the G1 phase of the cell cycle. Further characterization of the G1 defect indicates that the kinetics of cyclin D1 induction was delayed and that p27(KIP1) remains at higher levels for an extended period of time. Moreover, cells lacking TC-PTP showed a delayed activation of CDK2. This slow progression through the early G1-phase resulted in decreased phosphorylation of the RB protein and subsequent delay into the S phase transition. In contrast, no further defects were detected in other phases of the cell cycle. Survey of the potential signaling pathways leading to this delayed cyclin D1 expression indicated that NF-kappaB activation was compromised and that IKKbeta activity was also reduced following PDGF stimulation. Reintroduction of wild-type TC-PTP into the TC-PTP-/- cells rescued the defective proliferation, cyclin D1 expression, NF-kappaB activation as well as IkappaB phosphorylation. Together, these results confirm that TC-PTP plays a positive role in the progression of early G1 phase of the cell cycle through the NF-kappaB pathway. |
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Authors:
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M J Ibarra-Sánchez; J Wagner; M T Ong; C Lampron; M L Tremblay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 20 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-08-10 Completed Date: 2001-08-23 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 4728-39 Citation Subset: IM |
Affiliation:
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McGill Cancer Centre and Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals CDC2-CDC28 Kinases* Cell Cycle Proteins / metabolism Cell Division Cell Line Cells, Cultured Cyclin D1 / metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases / metabolism Embryo, Mammalian / cytology* Fibroblasts / cytology*, drug effects, metabolism G1 Phase Gene Deletion I-kappa B Kinase Kinetics Mice Mitogen-Activated Protein Kinase 1 / metabolism NF-kappa B / metabolism* Platelet-Derived Growth Factor / pharmacology Protein Tyrosine Phosphatase, Non-Receptor Type 2 Protein Tyrosine Phosphatases / genetics, physiology* Protein-Serine-Threonine Kinases / metabolism, physiology Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-akt Retinoblastoma Protein / metabolism Tumor Suppressor Proteins* |
| Chemical | |
Reg. No./Substance:
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0/Cdkn1b protein, mouse; 0/Cell Cycle Proteins; 0/NF-kappa B; 0/Platelet-Derived Growth Factor; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Tumor Suppressor Proteins; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.1.-/Chuk protein, mouse; EC 2.7.1.-/Ikbke protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.10/I-kappa B Kinase; EC 2.7.11.10/Ikbkb protein, mouse; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cdk2 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 2; EC 3.1.3.48/Protein Tyrosine Phosphatases; EC 3.1.3.48/Ptpn2 protein, mouse |
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