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rdf:type |
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lifeskim:mentions |
umls-concept:C0021745,
umls-concept:C0041904,
umls-concept:C0085103,
umls-concept:C0162493,
umls-concept:C0205263,
umls-concept:C0249586,
umls-concept:C1366765,
umls-concept:C1427559,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1879547
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pubmed:issue |
13
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
Interferon gamma (IFN-gamma) is a cytokine predominantly involved in antiproliferative and antiviral responses, immune surveillance, and tumor suppression. However, it has been shown that IFN-gamma is also involved in central nervous system development. Here we studied the underlying mechanism for IFN-gamma-induced neuronal differentiation using the human neuroblastoma Paju cell line. Our results indicate that IFN-gamma treatment led to neurite outgrowth followed by growth arrest in the G1 phase of the cell cycle. IFN-gamma induced ERK1/2 phosphorylation and subsequently the transcription factor early gene response 1, which in turn up-regulated p35 expression and increased cyclin-dependent kinase 5 (Cdk5) activity. IFN-gamma-induced neurite outgrowth was abolished by the treatment of MEK1/2 kinase inhibitors, such as U0126 and PD98059, which inhibit the ERK1/2 activation and subsequently prevent the up-regulation of p35 expression and Cdk5 activity. In agreement with the role of p35-Cdk5 in neuronal differentiation, small interfering RNA targeting Cdk5 abrogate the IFN-gamma-induced neurite outgrowth. Together, these results demonstrate for the first time that IFN-gamma-triggered neuronal differentiation mediated through the up-regulation of p35-associated Cdk5 depends on the activation of the ERK1/2 pathway. Therefore, the present study suggests that IFN-gamma is not only involved in tumorigenicity but also involved in neurogenesis by regulating cell proliferation and differentiation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/neuronal Cdk5 activator (p25-p35)
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12896-901
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15695523-Antibodies, Monoclonal,
pubmed-meshheading:15695523-Apoptosis,
pubmed-meshheading:15695523-Apoptosis Regulatory Proteins,
pubmed-meshheading:15695523-Blotting, Western,
pubmed-meshheading:15695523-Cell Cycle,
pubmed-meshheading:15695523-Cell Differentiation,
pubmed-meshheading:15695523-Cell Line, Tumor,
pubmed-meshheading:15695523-Cell Proliferation,
pubmed-meshheading:15695523-Cell Survival,
pubmed-meshheading:15695523-DNA, Complementary,
pubmed-meshheading:15695523-Dose-Response Relationship, Drug,
pubmed-meshheading:15695523-Enzyme Activation,
pubmed-meshheading:15695523-Flow Cytometry,
pubmed-meshheading:15695523-Humans,
pubmed-meshheading:15695523-Interferon-gamma,
pubmed-meshheading:15695523-Membrane Glycoproteins,
pubmed-meshheading:15695523-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15695523-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15695523-Nerve Tissue Proteins,
pubmed-meshheading:15695523-Neurons,
pubmed-meshheading:15695523-RNA, Small Interfering,
pubmed-meshheading:15695523-Signal Transduction,
pubmed-meshheading:15695523-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:15695523-Time Factors,
pubmed-meshheading:15695523-Transfection,
pubmed-meshheading:15695523-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15695523-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Interferon gamma induces neurite outgrowth by up-regulation of p35 neuron-specific cyclin-dependent kinase 5 activator via activation of ERK1/2 pathway.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Winship Cancer Institute, Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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