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The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR

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Item Type:Article
Title:The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR
Creators Name:Scharaw, S. and Iskar, M. and Ori, A. and Boncompain, G. and Laketa, V. and Poser, I. and Lundberg, E. and Perez, F. and Beck, M. and Bork, P. and Pepperkok, R.
Abstract:Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COPII) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COPII components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane.
Keywords:COP-Coated Vesicles, Carrier Proteins, Cell Membrane, Cell Nucleus, Endosomes, Epidermal Growth Factor, Golgi Apparatus, Green Fluorescent Proteins, HeLa Cells, Phosphatidylinositol 3-Kinases, Protein Transport, Proteolysis, Proto-Oncogene Proteins c-akt, Epidermal Growth Factor Receptor, Genetic Transcription, Up-Regulation
Source:Journal of Cell Biology
Publisher:Rockefeller University Press
Page Range:543-558
Date:21 November 2016
Official Publication:https://doi.org/10.1083/jcb.201601090
PubMed:View item in PubMed

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