Fig. 7
From: EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
EGFR regulation by RanBP6 (model). A (small) pool of EGF receptors functions as a scaffold for RanBP6-mediated nuclear import of STAT3. Nuclear STAT3 represses EGFR transcription. The solid lines between EGFR–STAT3–RanBP6 and RanBP6–Ran indicate protein–protein interactions (i.e., not necessarily direct molecular interactions). This mechanism of EGFR regulation serves to repress EGFR transcription at steady state and is inactivated when the cellular demand for EGFR transcription increases (e.g., following EGF-induced receptor protein degradation). Cancer cells inactivate this physiologic mechanism of EGFR regulation through deletion of the RANBP6 gene or silencing of PTEN (which disrupts the EGFR–RanBP6 interactions)
