Figure 4.
ER-associated degradation control of master transcriptional regulators of lipid metabolism. In the presence of sterols, Insigs mediate the ER retention of the SCAP-SREBP complex. In the absence of sterols, a gp78-UBXD8 complex degrades Insigs, and SCAP-SREBP traffics to the Golgi complex. In the Golgi complex, SREBP is proteolytically processed at two sites, releasing a soluble transcription factor that binds SRE sequences and induces expression of lipid-related genes. Abbreviations: ER, endoplasmic reticulum; gp78, glycoprotein 78; Insig, insulin-induced gene; SCAP, SREBP cleavage-activating protein; SRE, sterol regulatory element; SREBP, sterol regulatory element–binding protein; UBXD8, UBX domain–containing protein 8; VCP, valosin-containing protein.