Mig-6, signal transduction, stress response and cancer.
The mitogen-inducible gene-6 (Mig-6) is an immediate early response gene encoding a nonkinase scaffolding adaptor protein. Mig-6 gene expression can be rapidly and robustly induced under both normal and pathological scenarios by factors including hormones, growth factors, and stresses. However, the precise role of Mig-6 has virtually been a mystery until recently, when we and others discovered that Mig-6 may play important roles in regulating stress response, maintaining homeostasis in tissues like joints or cardiac muscle, and functioning as a tumor suppressor. The discovery that Mig-6 acts as a negative feedback inhibitor of EGF receptor signaling through a direct, physical interaction with the EGF receptor opens a door for understanding the mechanism underlying Mig-6 function. Yet how Mig-6 fine tunes or integrates signal transduction in many pathophysiological situations remains to be determined. Here we will highlight recent discoveries on the role of Mig-6 in stress response, tissue homeostasis, and cancer development; review the transcriptional regulation of Mig-6 expression; share insight into its mechanism in regulating signal transduction; and discuss the paradox of its action modes under different pathophysiological conditions.
Zhang
Yu-Wen
YW
Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, Michigan, USA. yu-wen.zhang@vai.org
Vande Woude
George F
GF
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C484017:ERRFI1 protein, human; D025521:Tumor Suppressor Proteins