Related Experiment Video
Updated: Jul 11, 2026
07:23
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Cooperation between STAT3 and c-jun suppresses Fas transcription.
V N Ivanov1, A Bhoumik, M Krasilnikov
1The Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Molecular Cell
|July 21, 2001
Summary
Melanoma progression often decreases Fas expression, hindering Fas-ligand (FasL)-induced apoptosis. Suppressing Stat3 or c-Jun increases Fas expression, restoring apoptosis and potentially improving cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Decreased Fas receptor expression in tumors limits Fas-ligand (FasL)-induced apoptosis, promoting tumor progression and metastasis.
- Melanoma exhibits an inverse relationship between Fas cell surface expression and its tumorigenicity and metastatic potential.
Purpose of the Study:
- To investigate the role of Signal Transducer and Activator of Transcription 3 (Stat3) and c-Jun in regulating Fas expression in melanoma.
- To determine if Stat3 and c-Jun influence melanoma cell sensitivity to FasL-mediated apoptosis.
Main Methods:
- Utilized dominant-negative Stat3 or c-Jun expression in human and mouse melanoma cells.
- Assessed Fas cell surface expression and sensitivity to FasL-induced apoptosis in genetically modified melanoma cells (Stat3+/- and c-Jun-/-).
- Investigated the mechanism of Fas expression suppression by Stat3 and c-Jun, distinguishing it from Stat3-mediated transcriptional activation.
Main Results:
- Expression of dominant-negative Stat3 or c-Jun significantly increased Fas expression and sensitized melanoma cells to FasL-induced apoptosis.
- Stat3+/- and c-Jun-/- melanoma cells showed elevated Fas surface expression and enhanced sensitivity to FasL.
- Stat3 and c-Jun suppress Fas expression through a mechanism independent of Stat3-mediated transcriptional activation.
Conclusions:
- Stat3 and c-Jun cooperate to downregulate Fas surface expression in melanoma.
- This downregulation of Fas by Stat3 and c-Jun contributes to tumor therapy resistance and metastasis.
- Targeting the Stat3-c-Jun interaction may represent a therapeutic strategy to restore Fas-mediated apoptosis in melanoma.
More Related Videos
11:19Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
10:16SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
Published on: January 6, 2017
Related Concept Videos
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...