Figure 1.

Graphic illustration of RIP mediated by S1P and S2P. Cholesterol deprivation triggers RIP of SREBP to activate genes required for cholesterol synthesis and uptake. Accumulation of unfolded proteins in the ER stimulates RIP of ATF6α to activate genes facilitating protein folding in the ER. Fasting-induced VLDL assembly triggers RIP of CREB3L3 to activate fasting-induced genes, including activators for LPL that hydrolyze VLDL particles. Cytokines of the TGF-β family and ceramide induce RIP of CREB3L1 to stimulate expression of genes that inhibit cell proliferation and that activate assembly of collagen-containing matrix. Chondrocyte differentiation stimulates RIP of CREB3L2 to activate genes encoding COPII components. The luminal C-terminal fragment of CREB3L2 released from S1P-catalyzed cleavage is secreted out of cells to stimulate proliferation of neighboring cells.