ERBB receptor feedback inhibitor 1 (MIG6) (ERRFI1)

ERBB receptor feedback inhibitor 1 (MIG6), also known as Mitogen-inducible gene 6, is a cytosolic scaffold protein that serves as a critical negative regulator of the Epidermal Growth Factor Receptor (EGFR) and other members of the ERBB family [1, 4]. It functions by binding to the kinase domain of these receptors, preventing their dimerization and subsequent activation of downstream signaling pathways like MAPK and PI3K/AKT [3]. In oncology, the loss or downregulation of MIG6 mRNA is a frequent event that leads to uncontrolled cell proliferation and resistance to EGFR tyrosine kinase inhibitors (TKIs), making its expression levels a vital biomarker for predicting patient response to drugs like erlotinib [3]. Beyond cancer, MIG6 plays a significant role in metabolic health; it has been identified as a mediator of endoplasmic reticulum stress-induced apoptosis in pancreatic beta cells [2]. Consequently, targeting MIG6 mRNA for inhibition is being explored as a therapeutic strategy to preserve beta-cell mass and function in the treatment of diabetes [2]. While no direct small-molecule inhibitors of MIG6 are currently approved, its modulation via mRNA-based technologies or induction by glucocorticoids represents a promising frontier in precision medicine [1, 2].

Other names

Mitogen-inducible gene 6ERRFI1Gene 33RALTReceptor-associated late transducer

MIG6 protein binds to the kinase domain of ERBB receptors, sterically inhibiting their activation and downstream signaling [3].