SREBP

Fatty acid synthesis 1 SREBP-1c, HNF-4a l Expression ACC1, fatty acid synthase Liver... 

Mutations within the SREBPs and the SREBP processing proteins (SCAP, SIP, S2P) have intensively been searched, especially in patients with familial hypercholesterolemia. So far, however, only four polymorphic sites within SCAP [38, 39], one within the promoter of SREBP-la [40], and five mutations in SREBP-2 [41] have been published. Yet, the impact of these polymorphisms and mutations on the response to statins has not been evaluated. 

Brown MS, Goldstein JL. The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997 89 331-340. 

Osborne TF. Sterol regulatory element binding protein (SREBPs) Key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000 275 32379-32382. 

Nakajima T, Ota N, Kodama T, Emi M. Isolation and radiation hybrid mapping of a highly polymorphic CA repeat sequence at the SREBP cleavage-activating protein (SCAP) locus. J Hum Genet 1999 44 350-351. 

Iwaki K, Nakajima T, Ota N, Emi M. A common Ile796Val polymorphism of the human SREBP cleavage-activating pro-... 

Vedie B, Jeunemaitre X, Megnien JL, Atger V, Simon A, Moatti N. A new DNA polymorphism in the 5 untranslated region of the human SREBP-la is related to development of atherosclerosis in high cardiovascular risk population. Atherosclerosis 2001 154 589-597. 

SREBP sterol regulatory element binding protein... 

It is SREBPs which coordinate the expression of HMG CoA reductase and cell surface receptors for LDL. Cholesterol is an essential component of membranes so if delivery of cholesterol to the cell is limited by low concentrations of LDL-cholesterol, the expression of the genes for both the LDL receptor and HMG CoA reductase are up-regulated allowing the cell to extract as much as possible form the circulation and also to synthesize cholesterol, thus there is an inverse relationship between plasma LDL-cholesterol concentration and HMG CoA reductase activity. 

FIGURE 21-43 SREBP activation. Sterol regulatory element-binding proteins (SREBPs, shown in green) are embedded in the ER when first synthesized, in a complex with the protein SREBP cleavage-activating protein (SCAP, red). (N and C represent the amino and carboxyl termini of the proteins.) When bound to SCAP, SREBPs are inactive. When... 

Includes a timely new discussion on the regulation of cholesterol metabolism at the genetic level, with consideration of sterol regulatory element-binding proteins (SREBPs). 

Regulation of HMG CoA reductase. SRE = sterol regulatory element SREBP = sterol regulatory elementbinding protein. 

Ye J., Rawson R. B., Kumoro R., Chen X. and Dave U. P. et al. (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell. 6, 1355-1364. 

SREBPs Sterol Receptor Element-Binding Proteins... 

Horton, J.D., Goldstein, J.L., Brown, M.S. 2002. SREBPs Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125-1131. 

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