Nuclear localization of EGF receptor and its potential new role as a transcription factor.
Epidermal growth factor receptor (EGFR) has been detected in the nucleus in many tissues and cell lines. However, the potential functions of nuclear EGFR have largely been overlooked. Here we demonstrate that nuclear EGFR is strongly correlated with highly proliferating activities of tissues. When EGFR was fused to the GAL4 DNA-binding domain, we found that the carboxy terminus of EGFR contained a strong transactivation domain. Moreover, the receptor complex bound and activated AT-rich consensus-sequence-dependent transcription, including the consensus site in cyclin D1 promoter. By using chromatin immunoprecipitation assays, we further demonstrated that nuclear EGFR associated with promoter region of cyclin D1 in vivo. EGFR might therefore function as a transcription factor to activate genes required for highly proliferating activities.
Lin
S Y
SY
Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Makino
K
K
Xia
W
W
Matin
A
A
Wen
Y
Y
Kwong
K Y
KY
Bourguignon
L
L
Hung
M C
MC
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001940:Breast; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002843:Chromatin / Q000502:physiology; D016384:Consensus Sequence; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000166:cytology / Q000378:metabolism
D002843:Chromatin; D011994:Recombinant Proteins; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors