SREBP SCAP

SREBP/SCAP not transported to Golgi SREBP processing blocked Site-2 Protease hmGR degradation accelerated... 

HMGR binds nsig/GP78 HMGR ubiquitinated SREBP/SCAP transported to Golgi SREBP processed... 

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. 

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. 

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... 

What are SREBP and SCAP What role do they play in the regulation of cholesterol homeostasis ... 

X. Hua, A. Nohturfft, J. L. Goldstein, and M. S. Brown. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage activating protein, (SCAP). Cett, 87, 415-426, 1996. 

Figure 1 S2P contains conserved HEXXH and LOG motifs found in metaiioproteases. SREBP first is cieaved by SI P in the iuminai ioop. The regulatory domain (Reg) interacts with the choiesteroi-sensing SCAP to ensure that SI P proteoiysis oniy occurs when choiesteroi ieveis are iow. Subsequent intramembrane proteoiysis reieases this transcription factor for the expression of genes essentiai to choiesteroi and fatty acid synthesis.

Nohturfft A, DeBose-Boyd RA, Scheek S, Goldstein JL, Brown MS. Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proc. Natl. Acad. Sci. U.S.A. 1999 96 11235-11240. 

P.A. Edwards, D. Tabor, H.R. Kast, and A. Venkateswaran. 2000. Regulation of gene expression by SREBP and SCAP Biochim. Biophys. Acta 1529 103-113. (PubMed)... 

SREBP resides in the endoplasmic reticulum, where it is bound to SCAP by its regulatory (Reg) domain. When cholesterol levels fall, SCAP and SREBP move to the Golgi complex, where SREBP undergoes successive proteolytic cleavages by a serine protease and a metalloprotease. The released DNA-binding domain moves to the nucleus to alter gene expression. [After an illustration provided by Dr. Michael Brown and Dr. Joseph Goldstein.]... 

Lipid homeostasis, Cholesterol biosynthesis HMG-CoA reductase, SCAP, SREBP, ACAT-1, ACAT-2, ACACA, ACACB, LXR-a, DGATl, LDLR, LRP2, ABCAl Hyperlipidemia, Dys-lipidemia, Obesity, Alzheimer s, Coronary heart disease, Atherosclerosis... 

A FIGURE 18-17 Model for cholesterol-sensitive control of SREBP activation mediated by insig-1 (2) and SCAP. The... 

Fig. 1.2 A schematic overview of the proteolytic processing of SREBPs. This pathway was described as a cholesterol-sensing process which applies to both SREBP-2 and SREBP-la. While SCAP and Insig are involved in the proteolytic cleavage of SREBP-lc the detailed mechanisms by which insulin regulates SREBP-lc processing are not known...

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