Exploration of the Biological Functionality of EGFR in the Nucleus

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved in cell proliferation, differentiation and survival. Aberrant expression and activation of EGFR have shown to cause various types of human tumors including breast, ovary, lung, head and neck, and frequently associated with poor prognosis. Upon the ligand binding and subsequent receptor dimmer formation activates protein tyrosine kinase then initiates several cellular signaling cascades. In addition to the role of initiator of traditional signal pathway, several reports have shown that EGFR is detected in the nucleus in several types of cells and tissues such as liver, placenta and thyroid. Nuclear EGFR has also been found in breast carcinoma and oropharyngeal squamous cell cancer and serves as a poor prognostic marker. Currently, it is known that nuclear EGFR is associated with transcription, DNA synthesis and DNA repair activity. However, the studies for the biological significances and functionalities of nuclear EGFR remain limited. In this proposal, using the nuclear localization sequence (NLS) identified within the EGFR, we will make the nuclear targeting deficiency and restored mutants in attempt to elucidate the specific biological functions of nuclear EGFR. Furthermore, we will identify and characterize the nuclear EGFR interacting proteins to explore the role of nuclear EGFR in transcriptional regulation and study novel function of nuclear EGFR. Finally, we will identify the novel nuclear target genes using systemic and non-bias approach to discover new functionality of nuclear EGFR. Success of this proposal will greatly extent our knowledge on the biological functionalities of nuclear EGFR and helps to discover new prognosis marker and develop new approach for tumor therapy.

Project ID:PC9808-0956
External Project ID:NSC98-2320-B182-037