title: RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
abstract: EGF induces the translocation of EGF receptor (EGFR) from the cell surface to the nucleus where EGFR activates gene transcription through its binding to an AT-rich sequence (ATRS) of the target gene promoter. However, how EGFR, without a DNA-binding domain, can bind to the gene promoter is unclear. In the present study, we show that RNA helicase A (RHA) is an important mediator for EGFR-induced gene transactivation. EGF stimulates the interaction of EGFR with RHA in the nucleus of cancer cells. The EGFR/RHA complex then associates with the target gene promoter through binding of RHA to the ATRS of the target gene promoter to activate its transcription. Knockdown of RHA expression in cancer cells abrogates the binding of EGFR to the target gene promoter, thereby reducing EGF/EGFR-induced gene expression. In addition, interruption of EGFR-RHA interaction decreases the EGFR-induced promoter activity. Consistently, we observed a positive correlation of the nuclear expression of EGFR, RHA, and cyclin D1 in human breast cancer samples. These results indicate that RHA is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Longfei
authors.initials: L
authors.lastname: Huo
authors.forename: Ying-Nai
authors.initials: YN
authors.lastname: Wang
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Hsu
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Hsu
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Huang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Ding
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D021581:Active Transport, Cell Nucleus; D001943:Breast Neoplasms / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; D004247:DNA; D066246:ErbB Receptors; D020365:RNA Helicases
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