Student and Faculty Publications
Publication Date
4-15-2023
Journal
American Journal of Cancer Resarch
Abstract
Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) in the EGFR NES led to increased nuclear accumulation of the protein via a less efficient release of the exportin CRM1. Interestingly, L747 with serine (L747S) and with proline (L747P) mutations were found in both tyrosine kinase inhibitor (TKI)-treated and -naïve patients with lung cancer who had acquired or de novo TKI resistance and a poor outcome. Reconstituted expression of the single NES mutant EGFR
Keywords
EGFR, nuclear translocation, activating mutations, NES, NLS, CRM1, exportin, internalization, non-small cell lung cancer
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Oncology Commons, Pulmonology Commons
Comments
Supplementary Materials
PMID: 37168336