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Published on: December 4, 2018
Nuclear epidermal growth factor receptor interacts with transcriptional intermediary factor 2 to activate cyclin D1
Yin Shi1, Yongguang Tao, Yiqun Jiang
1Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.
Abstract:
The epidermal growth factor receptor (EGFR), a ubiquitously expressed receptor tyrosine kinase, is an important factor in carcinogenesis. Transcriptional intermediary factor 2 (TIF2), a member of the p160 nuclear receptor co-activator gene family, is linked to the proliferation of cancer cells. However, the direct interplay between the EGFR and the nuclear receptors remains unclear. Our previous study demonstrated that nuclear EGFR could directly bind to the cyclin D1 promoter under the regulation of the oncoprotein latent membrane protein 1 (LMP1), but it also indicated that other factors are involved in the activation of target genes. In this study, we found that LMP1 upregulated the expression of TIF2 and promoted the interaction of EGFR with TIF2 in nasopharyngeal carcinoma. Furthermore, we demonstrated that the intact complex was linked with cyclin D1 promoter activity in an LMP1-dependent manner. The physiological functions of the intact complex were associated with cell proliferation and cell cycle progression. These findings suggest that TIF2 is a novel binding partner for nuclear EGFR and is involved in regulating its target gene expression.
Insights
Transcriptional intermediary factor 2 (TIF2) interacts with nuclear epidermal growth factor receptor (EGFR) in nasopharyngeal carcinoma, promoting cancer cell proliferation and cyclin D1 expression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase crucial in cancer development.
- Transcriptional intermediary factor 2 (TIF2) is a co-activator involved in cancer cell proliferation.
- The interaction between nuclear EGFR and nuclear receptors is not fully understood.
Purpose of the Study:
- To investigate the interplay between EGFR and TIF2 in nasopharyngeal carcinoma.
- To determine the role of latent membrane protein 1 (LMP1) in regulating this interaction.
- To elucidate the functional consequences of the EGFR-TIF2 complex on gene expression and cell behavior.
Main Methods:
- Western blotting to assess protein expression levels.
- Co-immunoprecipitation assays to detect protein-protein interactions.
- Reporter assays to measure promoter activity.
- Cell proliferation and cell cycle analysis.
Main Results:
- LMP1 upregulates TIF2 expression in nasopharyngeal carcinoma.
- LMP1 promotes the interaction between nuclear EGFR and TIF2.
- The EGFR-TIF2 complex binds to the cyclin D1 promoter in an LMP1-dependent manner.
- This complex enhances cyclin D1 promoter activity, driving cell proliferation and cell cycle progression.
Conclusions:
- TIF2 is identified as a novel binding partner for nuclear EGFR.
- The EGFR-TIF2 complex, regulated by LMP1, plays a significant role in nasopharyngeal carcinoma progression.
- Targeting this complex may offer a therapeutic strategy for nasopharyngeal carcinoma.
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