Nuclear epidermal growth factor receptor interacts with transcriptional intermediary factor 2 to activate cyclin D1 gene expression triggered by the oncoprotein latent membrane protein 1

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.