Figure 9.

Schematic diagram of lycorine. Sterols block the SCAP-SREBFs transport from the ER to the Golgi apparatus by sequestering the SCAP-SREBFs complex in the ER lumen, which is a potential risk factor of ER stress. Lycorine binds to SCAP at the WD40 domain, which leads to the dissociation of SCAP-SREBFs from INSIG1. Once SCAP leaves the ER, it is captured by SQSTM1 and escorted to the lysosome for degradation. When SCAP proteins are reduced, SREBFs undergoes ubiquitylation and proteasomal degradation, thus lipogenic gene expression is suppressed