RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.
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.
Huo
Longfei
L
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wang
Ying-Nai
YN
Xia
Weiya
W
Hsu
Sheng-Chieh
SC
Lai
Chien-Chen
CC
Li
Long-Yuan
LY
Chang
Wei-Chao
WC
Wang
Yan
Y
Hsu
Ming-Chuan
MC
Yu
Yung-Luen
YL
Huang
Tzu-Hsuan
TH
Ding
Qingqing
Q
Chen
Chung-Hsuan
CH
Tsai
Chang-Hai
CH
Hung
Mien-Chie
MC
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
C530104:CCND1 protein, human; D019938:Cyclin D1; D004247:DNA; D066246:ErbB Receptors; D020365:RNA Helicases
Oncogene. 2009 Oct 29;28(43):3801-13
19684613
Cancer Res. 2005 Jan 1;65(1):338-48
15665312
Eur J Nucl Med Mol Imaging. 2003 Oct;30(10):1348-56
12937952
Curr Opin Cell Biol. 2003 Apr;15(2):143-8
12648669
Mol Cell Biol. 2005 May;25(9):3784-92
15831482
Cell. 2009 Oct 30;139(3):610-22
19879846
J Biol Chem. 2004 Nov 12;279(46):47740-5
15358781
Nucleic Acids Res. 2008 Aug;36(13):4337-51
18586824
Clin Cancer Res. 2005 Aug 15;11(16):5856-62
16115926
Am J Transl Res. 2009 Mar 08;1(3):249-58
19956435
Pathobiology. 2007;74(1):15-21
17496429
Nucleic Acids Res. 2003 Oct 1;31(19):5741-53
14500838
Exp Cell Res. 2009 Feb 15;315(4):683-96
19278030
Mol Carcinog. 2009 Jul;48(7):610-7
19058255
Science. 2007 May 25;316(5828):1160-6
17525332
Cancer Res. 2007 Jun 1;67(11):5267-74
17545606
Clin Cancer Res. 2006 Jan 1;12(1):123-30
16397033
J Biol Chem. 1993 Aug 5;268(22):16822-30
8344961
Biochemistry. 1994 Apr 5;33(13):3906-12
7511411
Biochem Biophys Res Commun. 1985 Apr 30;128(2):898-905
2986629
Mol Cell Biol. 1998 Feb;18(2):1065-73
9448004
Genomics. 1998 Feb 1;47(3):365-71
9480750
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5
15302935
Cell. 1991 Sep 6;66(5):935-47
1653648
Br J Cancer. 2006 Jan 30;94(2):184-8
16434982
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6555-60
18006754
J Histochem Cytochem. 2000 Jan;48(1):21-33
10653583
Mol Carcinog. 2006 Jan;45(1):10-7
16299810
Nat Rev Cancer. 2008 Nov;8(11):835-50
18948996
Nat Cell Biol. 2001 Sep;3(9):802-8
11533659
Cancer Cell. 2005 Jun;7(6):575-89
15950906
J Biol Chem. 2007 Apr 6;282(14):10432-40
17283074
Trends Cell Biol. 2006 Dec;16(12):649-56
17085050
Nat Cell Biol. 2006 Dec;8(12):1359-68
17115032
Clin Cancer Res. 2009 Nov 1;15(21):6484-9
19861462
Eur J Biochem. 2004 Sep;271(18):3741-51
15355351
J Biol Chem. 2004 Apr 16;279(16):16657-61
14985334
J Nucl Med. 2007 Sep;48(9):1562-70
17704253
J Biol Chem. 2001 Jan 12;276(2):1634-42
11038348
Bioessays. 2000 Aug;22(8):697-707
10918300
Nucleic Acids Res. 2006;34(15):4206-15
16935882