Source:http://linkedlifedata.com/resource/pubmed/id/15217838
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2004-10-6
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| pubmed:abstractText |
Signal transducer and activator of transcription 1 (STAT1), a transcription factor known to participate in antiviral responses, acts as a tumor suppressor inhibiting cell growth and promoting apoptosis. To study the role of STAT1 in DNA damage-induced apoptosis in B lymphocytes, its active form, STAT1alpha, was specifically inhibited by the overexpression of STAT1beta, the STAT1alpha truncated inhibitory isoform. An episomal vector with a tetracycline-inducible bidirectional promoter was created to induce the expression of 2 proteins, STAT1beta and enhanced green fluorescence protein (EGFP). The same vector was used to overexpress STAT1alpha as a control. Expression of STAT1beta inhibited the phosphorylation, the DNA-binding activity, and the transcriptional activity of STAT1alpha, as well as the expression of STAT1alpha target genes such as p21WAF1/CIP1, TAP1, IRF1, and PKR. Inhibiting STAT1alpha by STAT1beta increased the growth rate of transfected cells and their resistance to fludarabine-induced apoptosis and cell cycle arrest. Overexpressing STAT1beta reversed the negative regulation of Mdm2 expression observed after treatment with interferon-gamma (IFN-gamma), which activates STAT1, or with fludarabine. Nuclear translocation of p53 after fludarabine treatment was decreased when STAT1beta was overexpressed, and it was increased when STAT1alpha was induced. Oligonucleotide pull-down experiments showed a physical STAT1/p53 interaction. Our results show that imbalance between the antiproliferative/proapoptotic isoform STAT1alpha and the proliferative isoform STAT1beta is likely to play a crucial role in the regulation of proliferation and apoptosis and that STAT1alpha may regulate p53 activity and sensitize B cells to fludarabine-induced apoptosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Vidarabine,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/fludarabine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
104
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2475-83
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15217838-Apoptosis,
pubmed-meshheading:15217838-B-Lymphocytes,
pubmed-meshheading:15217838-Cell Cycle,
pubmed-meshheading:15217838-Cell Division,
pubmed-meshheading:15217838-Cell Line,
pubmed-meshheading:15217838-DNA-Binding Proteins,
pubmed-meshheading:15217838-Down-Regulation,
pubmed-meshheading:15217838-Gene Expression,
pubmed-meshheading:15217838-Genetic Vectors,
pubmed-meshheading:15217838-Green Fluorescent Proteins,
pubmed-meshheading:15217838-Humans,
pubmed-meshheading:15217838-Nuclear Proteins,
pubmed-meshheading:15217838-Protein Binding,
pubmed-meshheading:15217838-Proto-Oncogene Proteins,
pubmed-meshheading:15217838-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:15217838-RNA, Messenger,
pubmed-meshheading:15217838-STAT1 Transcription Factor,
pubmed-meshheading:15217838-Trans-Activators,
pubmed-meshheading:15217838-Tumor Suppressor Protein p53,
pubmed-meshheading:15217838-Vidarabine
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| pubmed:year |
2004
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| pubmed:articleTitle |
Differential roles of STAT1alpha and STAT1beta in fludarabine-induced cell cycle arrest and apoptosis in human B cells.
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| pubmed:affiliation |
EA 3406 Université Paris 13, Service de Biochimie, Hôpital Avicenne, 125 route de Stalingrad, 93009 Bobigny Cedex, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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