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Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2
- Source :
- Oncogene. 22(23)
- Publication Year :
- 2003
-
Abstract
- The signal transducing protein Stat3 activates gene transcription in cells in response to multiple cytokines. Constitutive activation of Stat3 has been observed in solid tumors including head and neck squamous cell carcinoma. Stat3 activation in cancer has been associated with autocrine stimulatory loops and is believed to convey a growth advantage to cells. We now demonstrate ligand-independent activation of Stat3 by high cell density in multiple cancer cell lines. Activation of Stat3 is associated with antiproliferative rather than proliferative conditions. Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity. Our data supports a model in which Stat3 activity is partially suppressed by cdk2 in growing cells and derepressed upon cell confluence.
- Subjects :
- STAT3 Transcription Factor
rac1 GTP-Binding Protein
Cancer Research
Cell Communication
Protein Serine-Threonine Kinases
Mice
Downregulation and upregulation
Cyclin-dependent kinase
Genetics
CDC2-CDC28 Kinases
Roscovitine
Tumor Cells, Cultured
Animals
Humans
Enzyme Inhibitors
Phosphorylation
Autocrine signalling
STAT3
Molecular Biology
Mice, Knockout
Confluency
biology
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 2
3T3 Cells
Fibroblasts
Transforming Growth Factor alpha
Cyclin-Dependent Kinases
Cell biology
Up-Regulation
DNA-Binding Proteins
ErbB Receptors
Cell culture
Head and Neck Neoplasms
Purines
Cancer research
biology.protein
Carcinoma, Squamous Cell
Trans-Activators
Signal transduction
Cell Division
Signal Transduction
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 22
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....65f18ee8a551ae115b58b3666b6c50dc