Abstract
The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter- driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics*
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B-Lymphocytes / metabolism*
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Binding Sites / genetics
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Carrier Proteins*
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Cell Cycle Proteins*
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Cytokine Receptor gp130
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics*
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E2F Transcription Factors
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Gene Expression Regulation / genetics*
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Genes, Reporter / genetics
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Genes, myc / genetics*
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Membrane Glycoproteins / genetics*
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Mice
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Nuclear Proteins / analysis
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Promoter Regions, Genetic / genetics
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RNA, Messenger / genetics
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Receptors, Granulocyte Colony-Stimulating Factor / genetics
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Receptors, Interleukin-6 / genetics
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Retinoblastoma-Binding Protein 1
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STAT3 Transcription Factor
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Signal Transduction
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Trans-Activators / genetics*
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Transcription Factor DP1
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Transcription Factors / genetics
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Transcription, Genetic / genetics
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Transcriptional Activation
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Transfection / genetics
Substances
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Antigens, CD
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Arid4a protein, mouse
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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E2F Transcription Factors
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Il6st protein, mouse
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Membrane Glycoproteins
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Nuclear Proteins
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RNA, Messenger
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Receptors, Granulocyte Colony-Stimulating Factor
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Receptors, Interleukin-6
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Retinoblastoma-Binding Protein 1
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Transcription Factor DP1
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Transcription Factors
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Cytokine Receptor gp130