RNA 解旋酶 A 是 EGFR 介导的核内转录激活的 DNA 结合伴侣。
RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
机构信息
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16125-30. doi: 10.1073/pnas.1000743107. Epub 2010 Aug 27.
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.
表皮生长因子（EGF）诱导表皮生长因子受体（EGFR）从细胞膜转位到细胞核，在细胞核中，EGFR 通过与其靶基因启动子上富含 AT 的序列（ATRS）结合来激活基因转录。然而，没有 DNA 结合域的 EGFR 如何能与基因启动子结合尚不清楚。在本研究中，我们表明 RNA 解旋酶 A（RHA）是 EGFR 诱导基因转录激活的重要介质。EGF 刺激癌细胞核中 EGFR 与 RHA 的相互作用。然后，EGFR/RHA 复合物通过 RHA 与靶基因启动子上的 ATRS 结合，与靶基因启动子结合，从而激活其转录。在癌细胞中敲低 RHA 的表达会破坏 EGFR 与靶基因启动子的结合，从而减少 EGF/EGFR 诱导的基因表达。此外，中断 EGFR-RHA 相互作用会降低 EGFR 诱导的启动子活性。一致地，我们观察到人类乳腺癌样本中核表达的 EGFR、RHA 和细胞周期蛋白 D1 之间存在正相关。这些结果表明，RHA 是 EGFR 介导的核内转录激活的 DNA 结合伴侣。
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