MID-1 is a MG53-IRS-1 interaction disruptor. It abolished MG53-mediated IRS-1 ubiquitination and degradation, as well as sensitized insulin signaling and increased insulin-elicited glucose uptake with an elevated level of IRS-1 in C2C12 myotubes. MID-1 (5 μM; 24 h) increases the IRS-1 expression level in skeletal muscle by disrupting the MG53-IRS-1 interaction. MID-1 (10 μM; 12 h) reduces the luciferase activity in HEK 293 cell line expressing NLUC-IRS-1 and CLUC-C14A. MID-1 (1-20 μM; 12 h) disrupts the MG53-IRS-1 interaction but not MG53-FAK interaction in HEK 293 cells. MID-1 (0.1-10 μM; 4-24 h) abolishes MG53-induced IRS-1 ubiquitination and degradation in HEK 293 cells. MID-1 (5-10 μM; 24 h) increases insulin signaling and insulin-elicited glucose uptake in C2C12 myotubes. MID-1 (5-10 μM; 24 h) enhances skeletal myogenesis[2]. NCS-1 (neuronal calcium sensor-1) binds to the Ca2+ permeable channel MID-1 for tolerance to Ca2+ stress. CRZ-1 binds to a unique sequence in the ncs-1 promoter, causing upregulation of NCS-1 that binds to MID-1 for tolerance to Ca2+ stress[3].
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