TY  - JOUR
A1  - Scharaw, Sandra
A1  - Iskar, Murat
A1  - Ori, Alessandro
A1  - Boncompain, Gaelle
A1  - Laketa, Vibor
A1  - Poser, Ina
A1  - Lundberg, Emma
A1  - Perez, Franck
A1  - Beck, Martin
A1  - Bork, Peer
A1  - Pepperkok, Rainer
T1  - The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR
JF  - Journal of Cell Biology
N2  - 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 (COP II) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COP II 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.
KW  - Epidermal growth-factor
KW  - finger protein 11
KW  - receptor tyrosine kinases
KW  - early secretory pathway
KW  - breast-cancer
KW  - brefeldin-a
KW  - E3 ligase
KW  - trafficking
KW  - export
KW  - endoplasmic-reticulum
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186731
VL  - 215
IS  - 4
ER  -