title: 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.
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.
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Shi
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Tao
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.forename: Lanbo
authors.initials: L
authors.lastname: Xiao
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000235:genetics*; D017931:DNA Primers; D066246:ErbB Receptors / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D015513:Oncogene Proteins; D019938:Cyclin D1; D066246:ErbB Receptors