RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus

Longfei Huo, Ying Nai Wang, Weiya Xia, Sheng Chieh Hsu, Chien Chen Lai, Long Yuan Li, Wei Chao Chang, Yan Wang, Ming Chuan Hsu, Ng Luen Yu, Tzu Hsuan Huang, Qingqing Ding, Chung Hsuan Chen, Chang Hai Tsai, Mien Chie Hung*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

92 Scopus citations

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.

Original languageEnglish
Pages (from-to)16125-16130
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number37
DOIs
StatePublished - 14 09 2010
Externally publishedYes

Keywords

  • Cyclin D1
  • Inducible nitric oxide synthase
  • Nuclear translocation
  • Transcription

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