Dual regulation of the LDL receptor—Some clarity and new questions Alan D. Attie, Nabil G. Seidah  Cell Metabolism  Volume 1, Issue 5, Pages 290-292 (May 2005) DOI: 10.1016/j.cmet.2005.04.006 Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 1 Regulation of the LDL receptor Both the LDL receptor (LDLR) and PCSK9 genes are positively regulated by the nuclear form of SREBP-2 (nSREBP-2). The proteolytic release of nSREBP-2 from the ER is favored under conditions of sterol depletion as occurs with statins, drugs that inhibit de novo cholesterol synthesis. Increased expression of the LDLR mRNA leads to increased synthesis of LDLR protein. However, increased production of PCSK9 paradoxically enhances the degradation of LDLR protein. Thus, sterol depletion leads to two opposing effects on LDLR protein. Cell Metabolism 2005 1, 290-292DOI: (10.1016/j.cmet.2005.04.006) Copyright © 2005 Elsevier Inc. Terms and Conditions