RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
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| 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.
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| Authors | Longfei Huo, Ying-Nai Wang, Weiya Xia, Sheng-Chieh Hsu, Chien-Chen Lai, Long-Yuan Li, Wei-Chao Chang, Yan Wang, Ming-Chuan Hsu, Yung-Luen Yu, Tzu-Hsuan Huang, Qingqing Ding, Chung-Hsuan Chen, Chang-Hai Tsai, Mien-Chie Hung |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 37 Pg. 16125-30 (Sep 14 2010) ISSN: 1091-6490 [Electronic] United States |
| PMID | 20802156 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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