Show simple item record

dc.contributor.advisorMellinghoff, Ingo
dc.contributor.authorHsieh, Wan-Ying
dc.description.abstractThe epidermal growth factor receptor (EGFR) regulates many key biological processes including cell proliferation, survival and differentiation. It is frequently altered or amplified in cancers. Regulation of physiological EGFR function occurs at multiple levels, such as negative feedback regulation. We previously identified RAN-Binding Protein 6 (RanBP6), a protein of unknown functions, as a candidate EGFR interactor from an EGFR interactome study. Here, we validated that RanBP6, a member of the importin ? superfamily, interacts with EGFR and the proteins involved in nucleo-cytoplasmic transport. In addition, depletion of RanBP6 raised EGFR mRNA and protein levels, and upregulated EGFR promoter activity. Further studies revealed that RanBP6 represses EGFR transcription by modulating the subcellular localization of Signal transducer and activator of transcription 3 (STAT3). Focal deletions of the RANBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM). Silencing of RanBP6 promoted glioma growth in vivo and conferred resistance to EGFR tyrosine kinase inhibitors. Lastly, examination of RanBP6 substrates suggested RanBP6 is an importin for many tumor suppressors or oncoproteins. Our results demonstrated that RanBP6 functions as a novel EGFR feedback regulator to maintain EGFR homeostasis, and an importin for cancer-associated cargoes.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.subjectnucleo-cytoplasmic transport
dc.titleCharacterization Of Ran-Binding Protein 6 As A Novel Regulator Of The Epidermal Growth Factor Receptor
dc.typedissertation or thesis Cornell Graduate School of Medical Sciences of Philosophy

Files in this item


This item appears in the following Collection(s)

Show simple item record

Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International