Fig. 1. Diagrammatic representation of the ATF6 and SREBP activation by MBTPS2.

ATF6 and SREBP are synthesised in their inactive precursor forms and are embedded in the endoplasmic reticulum. ER stress and lipid/cholesterol deprivation can trigger the release of ATF6 and SREBPs, respectively. These inactive proteins are trafficked to the Golgi where they are sequentially cleaved by S1P and MBTPS2. Cleavage results in the release of mature, transcriptionally active proteins which are then shuttled to the nucleus. Here, ATF6 can bind and activate expression of ER-stress response genes, whereas SREBP activate expression of lipid and cholesterol metabolism.