مورد إلكتروني
Nucleocytoplasmic shuttling of persistently activated STAT3.
| العنوان: | Nucleocytoplasmic shuttling of persistently activated STAT3. |
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| بيانات النشر: | 2007 |
| تفاصيل مُضافة: | Herrmann, Andreas Vogt, Michael Monnigmann, Martin Clahsen, Thomas Sommer, Ulrike Haan, Serge Poli, Valeria Heinrich, Peter C. Muller-Newen, Gerhard |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Persistent activation of the transcription factor STAT3 has been detected in many types of cancer and plays an important role in tumor progression, immune evasion and metastasis. To analyze persistent STAT3 activation we coexpressed STAT3 with v-Src. We found that tyrosine phosphorylation of STAT3 by v-Src is independent of Janus kinases (Jaks), the canonical activators of STATs. The STAT3-induced feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), did not interfere with STAT3 activation by v-Src. However, the protein inhibitor of activated STAT3 (PIAS3) suppressed gene induction by persistently activated STAT3. We measured nucleocytoplasmic shuttling of STAT3 in single cells by bleaching the YFP moiety of double-labelled STAT3-CFP-YFP in the cytoplasm. Analysis of the subcellular distribution of CFP and YFP fluorescence over time by mathematical modeling and computational parameter estimation revealed that activated STAT3 shuttles more rapidly than non-activated STAT3. Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis. We propose passage of persistently activated STAT3 through the nuclear pore complex as a new target for intervention in cancer. |
| مصطلحات الفهرس: | Active Transport, Cell Nucleus/physiology, Animals, COS Cells, Cercopithecus aethiops, Cytoplasm/genetics/metabolism, Humans, Karyopherins/genetics/metabolism, Mice, Models, Biological, Molecular Chaperones/genetics/metabolism, NIH 3T3 Cells, Nuclear Pore/genetics/metabolism, Oncogene Protein pp60(v-src)/genetics/metabolism, Phosphorylation, Protein Inhibitors of Activated STAT/genetics/metabolism, Receptors, Cytoplasmic and Nuclear/genetics/metabolism, STAT3 Transcription Factor/genetics/metabolism, Suppressor of Cytokine Signaling Proteins/genetics/metabolism, info:eu-repo/semantics/article |
| DOI: | 10.1242.jcs.03482 |
| URL: | |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| أرقام أخرى: | LULUX oai:orbilu.uni.lu:10993/775 WOS:000249559400011 PMID: 17726064 SCOPUS_ID:35549007501 DOI:10.1242/jcs.03482 1134901323 |
| المصدر المساهم: | UNIV OF LUXEMBOURG From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1134901323 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1242.jcs.03482 |
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