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. 2000 Jun 6;97(12):6340–6344. doi: 10.1073/pnas.97.12.6340

Figure 1.

Figure 1

Model for SREBP-dependent gene activation. A schematic representation of key steps in activation of the LDL receptor promoter by SREBP and Sp1. The model depicts full-length SREBP tethered to the endoplasmic reticulum membrane through its two-pass membrane spanning domain. On sterol depletion, the protein is clipped out of the membrane and migrates to the nucleus, where it binds to the SREBP site in the LDL receptor promoter adjacent to an Sp1 site. This stimulates Sp1 to bind to the adjacent site, whereon the DNA bound Sp1 leads to a destablilization of DNA-bound SREBP (5). After it falls off the DNA, SREBP is rapidly degraded by a nuclear calpain type of protease activity (27). Under this model, the activation of the LDL receptor promoter by SREBP is transient and rapidly reversible, unless processing continues and SREBP levels continue to increase because of a chronic low cellular sterol level.