The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR.
Sandra ScharawMurat IskarAlessandro OriGaelle BoncompainVibor LaketaIna PoserEmma LundbergFranck PerezMartin BeckPeer BorkRainer PepperkokPublished in: The Journal of cell biology (2016)
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.
Keyphrases
- growth factor
- small cell lung cancer
- epidermal growth factor receptor
- tyrosine kinase
- transcription factor
- endoplasmic reticulum
- cell surface
- single cell
- gene expression
- induced apoptosis
- cell therapy
- genome wide
- stem cells
- cell cycle arrest
- dna methylation
- mesenchymal stem cells
- dna damage
- signaling pathway
- binding protein
- dna damage response
- endoplasmic reticulum stress
- oxide nanoparticles