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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
TAF4b and Jun/activating protein-1 collaborate to regulate the expression of integrin alpha6 and cancer cell
Margarita Kalogeropoulou1, Angeliki Voulgari, Vassiliki Kostourou
1Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Abstract:
The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific interactions between Jun family members and TATA box binding protein-associated factors (TAF) in colon HT29 adenocarcinoma cells. Particularly, TAF4b and c-Jun were found to colocalize and interact in the nucleus of advanced carcinoma cells and in cells with epithelial-to-mesenchymal transition (EMT) characteristics. TAF4b was found to specifically regulate the AP-1 target gene involved in EMT integrin alpha6, thus altering related cellular properties such as migration potential. Using a chromatin immunoprecipitation approach in colon adenocarcinoma cell lines, we further identified a synergistic role for TAF4b and c-Jun and other AP-1 family members on the promoter of integrin alpha6, underlining the existence of a specific mechanism related to gene expression control. We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT.
Insights
The TAF4b transcription factor interacts with AP-1 proteins, regulating genes like integrin alpha6 in colon cancer cells. This interaction is crucial for gene expression control during cancer progression and epithelial-to-mesenchymal transition (EMT).
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Transcription factor IID (TFIID) subunit TAF4b is vital for transcription initiation by RNA polymerase II.
- Activating protein-1 (AP-1) family members regulate genes involved in oncogenic transformation.
- Understanding TAF4b and AP-1 interactions is key to deciphering cancer-related gene expression.
Purpose of the Study:
- To investigate the interaction between TAF4b and AP-1 family members in colon adenocarcinoma cells.
- To elucidate the role of TAF4b and AP-1 in regulating target genes associated with cancer progression and EMT.
- To identify the mechanism of TAF4b and AP-1 in promoter recognition and transcription initiation.
Main Methods:
- Immunoprecipitation of endogenous protein complexes to detect protein-protein interactions.
- Confocal microscopy to visualize colocalization of TAF4b and c-Jun in cancer cells.
- Chromatin immunoprecipitation (ChIP) to identify TAF4b and AP-1 binding to target gene promoters.
Main Results:
- Specific interactions were identified between Jun family members and TAFs in HT29 colon adenocarcinoma cells.
- TAF4b and c-Jun colocalize and interact in the nucleus of advanced carcinoma cells and cells exhibiting EMT.
- TAF4b regulates the AP-1 target gene integrin alpha6, impacting cell migration, and shows a synergistic role with AP-1 on the integrin alpha6 promoter.
Conclusions:
- TAF4b and AP-1 family members interact and cooperate in regulating gene expression, specifically the integrin alpha6 gene.
- This interdependence is critical for cell type-specific promoter recognition and transcription initiation in cancer progression and EMT.
- The findings reveal a novel mechanism involving TAF4b and AP-1 in controlling gene expression during cancer development.
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